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        <title>Frontiers in Immunology | Inflammation section | New and Recent Articles</title>
        <link>https://www.frontiersin.org/journals/immunology/sections/inflammation</link>
        <description>RSS Feed for Inflammation section in the Frontiers in Immunology journal | New and Recent Articles</description>
        <language>en-us</language>
        <generator>Frontiers Feed Generator,version:1</generator>
        <pubDate>2026-05-13T15:25:47.743+00:00</pubDate>
        <ttl>60</ttl>
        <item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fimmu.2026.1824573</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fimmu.2026.1824573</link>
        <title><![CDATA[Beyond the usual suspects: rethinking post-stroke immunosuppression]]></title>
        <pubdate>2026-05-13T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Laia Ascaso-Vidal</author><author>Alba Simats</author><author>David Brea</author>
        <description><![CDATA[Ischemic stroke extends far beyond the hyperacute vascular event. In addition to the immediate ischemic injury, patients frequently develop systemic complications that significantly influence outcome. Among these, a biphasic immune response has emerged as a central feature: an early inflammatory reaction followed by a state of peripheral immunosuppression. This immunosuppressive phase has been consistently associated with increased susceptibility to post-stroke infections, particularly pneumonia, thereby contributing to morbidity and mortality. Multiple mechanisms have been implicated in the development of stroke-induced immunosuppression, including activation of the autonomic nervous system and the hypothalamic-pituitary-adrenal axis, the release of damage-associated molecular patterns (DAMPs), reprogramming of bone marrow hematopoiesis, and peripheral neutrophil activation with downstream effects on lymphocyte survival. While these pathways are often studied in isolation, accumulating evidence suggests that they may interact within a coordinated neuroimmune network. In this review, we not only summarize the current understanding of the mechanisms underlying post-stroke immunosuppression but also explore how these processes may converge and influence one another. Finally, we discuss the unresolved question of whether this immunosuppressive state represents an adaptive response aimed at protecting the injured brain or a maladaptive bystander consequence of disrupted neuroimmune homeostasis.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fimmu.2026.1792996</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fimmu.2026.1792996</link>
        <title><![CDATA[miRNA profiling shows shared signatures in pediatric asthma, obesity and their comorbidity]]></title>
        <pubdate>2026-05-13T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Harshita Shailesh</author><author>Mohamed Nadhir Djekidel</author><author>Safa Noor</author><author>Lena Hayati</author><author>Stefan Worgall</author><author>Souhaila Al Khodor</author><author>Ibrahim Janahi</author>
        <description><![CDATA[RationaleChildhood obesity is a known risk factor for asthma and contributes to increased disease severity and reduced corticosteroid responsiveness. However, the molecular mechanisms underlying this comorbidity remain unclear. Using a cross-sectional design, we aimed to identify microRNA (miRNA) signatures associated with asthma–obesity comorbidity in children to shed light on potential shared molecular drivers.MethodsWhole blood samples were collected from four pediatric groups: normal weight with asthma (NW-A, n = 11), overweight/obesity with asthma (OO-A, n = 10), overweight/obesity without asthma (OO, n = 10), and normal weight without asthma (NW, n = 12). Circulating miRNA profiles were assessed using the NanoString nCounter platform. Differential expression and pathway enrichment analyses were performed using Enrichr and other bioinformatic tools. Correlation with clinical and cytokine data was assessed by Pearson’s correlation and multiple regression analyses.ResultsmiRNA expression profiles differed markedly across the four groups. Five miRNAs (miR- 423-3p, -92a-3p, -4536-5p, -197-3p, -891a-5p) were consistently upregulated, and two (miR-144-3p, -641) were downregulated across asthma alone, obesity alone, and asthma-obesity comorbidity. Target gene analysis of OO-A-associated miRNAs highlighted involvement in IL-4, IL-13, and PIP3/AKT signaling, as well as pathways linked to innate immunity and metabolism. In OO-A, miRNA dysregulation was correlated with elevated neutrophils, pro-inflammatory cytokines, and reduced lung function.ConclusionIn this exploratory study, we identified a shared circulating miRNA signature in asthma–obesity comorbidity. These miRNAs may serve as biomarkers and potential therapeutic targets for stratifying and managing asthma in children with obesity, pending validation in longitudinal studies.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fimmu.2026.1826191</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fimmu.2026.1826191</link>
        <title><![CDATA[Neutrophil extracellular traps in gout: from immune defense to pathological dynamic equilibrium]]></title>
        <pubdate>2026-05-13T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Fangfang Wang</author><author>Ning Tie</author><author>Yong Jin</author><author>Hongbin Li</author>
        <description><![CDATA[Gout is an aseptic inflammatory disease caused by monosodium urate (MSU) crystal deposition. Its clinical signs go beyond the intense pain of acute arthritis to include structural damage such as chronic synovitis, bone erosion, and tophus formation. The long-term progression and recurring episodes of inflammation pose significant challenges in managing the disease. While hyperuricemia creates the metabolic basis, only a small percentage of patients develop gout, indicating that activation of the innate immune system is essential for its development. Recently, neutrophil extracellular traps (NETs) have become recognized as key mediators connecting metabolic issues to inflammatory responses, representing an important breakthrough in understanding gout pathogenesis. Initially, NETs are considered a host defense mechanism that protects against microbial invasion, where neutrophils release a web-like structure made of chromatin fibers and granular proteins to trap and eliminate microbes. However, in gout, a non-infectious disease, NETs have roles that extend beyond their traditional function, acting as a “double-edged sword”: they help limit acute inflammation but can also contribute to tissue damage and disease progression during the chronic phase, with their function changing according to the microenvironment. This review systematically discusses the mechanisms of NETs in gout development and examines their potential in diagnosing and treating the disease.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fimmu.2026.1835934</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fimmu.2026.1835934</link>
        <title><![CDATA[Lactate dehydrogenase-to-albumin ratio as a potential prognostic indicator in glucocorticoid-treated severe pneumonia: a multicenter retrospective study with external validation]]></title>
        <pubdate>2026-05-13T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Jiayi Lin</author><author>Jianyi Chen</author><author>Zhuolin Liu</author><author>Qiuhong Wen</author><author>Zetao Zheng</author><author>Xueyi Liu</author><author>Zijian Zhu</author><author>Danfeng Yang</author><author>Ziyi Zhou</author><author>Dakai Xiao</author><author>Chunli Liu</author>
        <description><![CDATA[BackgroundGlucocorticoids are widely used in severe pneumonia but can mask clinical symptoms and traditional severity scores. The lactate dehydrogenase-to-albumin ratio (LAR) reflects the balance between tissue injury and metabolic reserve, yet its prognostic value in steroid-treated pneumonia remains undefined.MethodsThis multicenter study utilized a primary cohort (n=500) and an independent external validation cohort (n=354) of pneumonia patients receiving glucocorticoid therapy. The primary endpoints were 30-day and 90-day all-cause mortality. We employed Cox regression, restricted cubic splines (RCS), and ROC analysis to evaluate LAR performance.ResultsHigh admission LAR (≥10.48) was identified as a potential prognostic indicator of mortality, associated with a more than twofold risk increase at 30 days (Adjusted HR 2.54; 95% CI: 1.56-4.12) and 90 days (Adjusted HR 2.44; 95% CI: 1.56-3.82). RCS analysis confirmed a non-linear risk escalation with a biological threshold of 10.22 (P non-linearity < 0.001). LAR demonstrated improved predictive discrimination (AUC 0.742) compared to PSI (AUC 0.700) and CURB-65 (AUC 0.654). Although the high LAR group received lower median cumulative glucocorticoid doses (3.0g vs. 5.8g; P < 0.001), this finding was associated with more rapid clinical progression and truncated treatment windows in high-risk patients, reflecting a survival-time-dependent exposure rather than a lack of therapeutic intensity.ConclusionsAdmission LAR is a potential, easily accessible biochemical marker that provides prognostic value independent of typical inflammatory signs masked by steroids. In patients exceeding the 10.22 threshold, our findings suggest a potential efficacy bottleneck for conventional steroid dosing, highlighting a high-risk subpopulation that may require optimized early intervention.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fimmu.2026.1827181</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fimmu.2026.1827181</link>
        <title><![CDATA[Convergent death programs in chronic obstructive pulmonary disease: how pyroptotic and ferroptotic crosstalk reshapes therapeutic paradigms]]></title>
        <pubdate>2026-05-13T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Aisi Huang</author><author>Shiming Liu</author><author>Jiao Lan</author>
        <description><![CDATA[Chronic obstructive pulmonary disease (COPD) remains a leading cause of global mortality, yet current therapies principally target bronchodilation and broad anti-inflammatory suppression rather than the regulated cell death programs driving tissue destruction. Pyroptosis, executed through inflammasome-driven gasdermin pore formation, and ferroptosis, mediated by iron-catalyzed lipid peroxidation upon GPX4 failure, have each been implicated in COPD pathogenesis but are conventionally treated as independent processes. This review advances three original contributions. First, we map pyroptotic and ferroptotic associations across COPD inflammatory endotypes, demonstrating preferential non-canonical pyroptotic engagement in T2-low neutrophilic disease and dual death-modality involvement in T2-high eosinophilic disease. Second, we delineate a hierarchical relationship—now supported in COPD-relevant epithelial systems—in which smoke-induced Nrf2 epigenetic silencing drives ferroptotic lipid peroxide accumulation that directly triggers pyroptotic execution through caspase-11 activation, positioning GPX4 as the molecular gatekeeper. Third, we propose an inverted U-shaped model reconciling paradoxical effects of lipid peroxidation on inflammasome regulation, where membrane phospholipid hydroperoxides drive activation while free cytosolic 4-hydroxynonenal mediates suppression through covalent NLRP3 modification. We further integrate extracellular trap biology as a convergent death-associated program sharing execution machinery with pyroptosis and ferroptosis. Building on this framework, we critically appraise emerging therapeutics—including dupilumab, anti-alarmin biologics, NLRP3 inhibitors, and ferroptosis-directed agents—and propose a biomarker-guided precision medicine strategy matching cell death-targeting therapies to individual inflammatory profiles. This framework reframes COPD therapeutic design from single-pathway inhibition toward integrated modulation of interconnected death programs stratified by inflammatory endotype.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fimmu.2026.1818375</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fimmu.2026.1818375</link>
        <title><![CDATA[Exploring potential value of neutrophil extracellular traps in major depressive disorder]]></title>
        <pubdate>2026-05-12T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Yachen Shi</author><author>Gaojia Zhang</author><author>Yi Ji</author><author>Guangjun Xi</author><author>Yiping You</author><author>Jingyu Deng</author><author>Qianqian Gao</author><author>Haixia Mao</author><author>Xuefang Lu</author><author>Xiaoxuan Zhang</author><author>Wei Ji</author><author>Xiaohang Wang</author><author>Pan Wang</author><author>Mengmeng Zhong</author><author>Yan Han</author><author>Peng Yuan</author><author>Xiangming Fang</author><author>Feng Wang</author>
        <description><![CDATA[BackgroundNeutrophil extracellular traps (NETs) can induce cellular and tissue damage through inflammatory responses. While the involvement of NETs in psychiatric disorders has shown preliminary potential, a systematic exploration of their link with major depressive disorder (MDD) is imperative. This study evaluated the clinical potential of three NET markers—myeloperoxidase (MPO)-DNA, neutrophil elastase (NE)-DNA, and citrullinated histones (citH3)—for diagnosing MDD and predicting treatment response.MethodsTwo independent clinical cohorts (Cohort 1: n=83; Cohort 2: n=60) and a chronic unpredictable mild stress (CUMS) mouse model were used. Physiotherapy and pharmacotherapy were administered to the two cohorts, respectively. NET markers were measured in plasma samples. Levels of NETs in the hippocampus were detected in CUMS mice. Pharmacological blockade of NET formation was performed in mice.Results(1) Independently validated across two cohorts, plasma levels of NET markers were significantly higher in MDD patients than in healthy participants. (2) In MDD patients, plasma NET markers significantly correlated with neuropsychological assessment scores, serum levels of inflammatory indices, and abnormal activation of the right calcarine and cuneus. (3) Relationship between NETs and C-reactive protein has an significant effect on depressive symptoms. (4) These NET markers could predict changes in 24-item Hamilton Depression Rating Scale scores after antidepressive treatments. (5) Compared with controls, CUMS mice exhibited significantly elevated levels of NE and MPO in the hippocampus. Preventing NET formation significantly reduced NE and MPO levels in plasma and hippocampus, and alleviated depressive-like behavior in CUMS mice.ConclusionsPlasma NETs may be associated with the occurrence and progression of MDD, potentially via inflammatory mechanisms. Plasma NET markers may be used as valuable biomarkers to diagnose MDD and predict patient response to antidepressive treatment. Targeting NET formation could represent a potential therapeutic strategy for depression.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fimmu.2026.1796827</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fimmu.2026.1796827</link>
        <title><![CDATA[Neutrophil extracellular traps and pyroptosis: a molecular nexus linking systemic autoimmune diseases to atherosclerosis]]></title>
        <pubdate>2026-05-12T00:00:00Z</pubdate>
        <category>Mini Review</category>
        <author>Yan Du</author><author>Lulu Zhang</author><author>Yiheng Cheng</author><author>Sijie Lu</author><author>Ronghua Ou</author><author>Xiaojian Deng</author>
        <description><![CDATA[This review aims to elucidate the molecular mechanisms of neutrophil extracellular traps (NETs) and pyroptosis, exploring their synergistic role as a pathological nexus bridging systemic autoimmune diseases with atherosclerosis. By systematically synthesizing recent literature and experimental evidence, we delineate the signaling cascades of these programmed inflammatory processes and analyze their contributions to disease progression in systemic lupus erythematosus, rheumatoid arthritis, and cardiovascular pathology. The analysis reveals a sophisticated bidirectional crosstalk, termed the NET-pyroptosis axis, which functions as a self-amplifying inflammatory loop that drives chronic tissue injury. Key findings highlight that while Gasdermin D serves as a context-dependent amplifier of NET release rather than a universal executioner, the Gasdermin E-mediated interaction between immune and stromal cells emerges as a critical driver of structural damage, such as synovial bone erosion and endothelial plaque denudation. Furthermore, we summarize emerging therapeutic strategies, including the pharmacological inhibition of peptidylarginine deiminase 4 and gasdermin pore formation, which hold significant promise for mitigating both systemic inflammation and the associated cardiovascular burden. Ultimately, this review establishes a novel pathophysiological framework that explains the heightened cardiovascular risk in autoimmune populations and provides a rationale for cross-disciplinary clinical interventions. Targeting the reciprocal interaction between these two inflammatory pathways may offer transformative breakthroughs in improving the long-term prognosis of patients with chronic inflammatory disorders.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fimmu.2026.1761552</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fimmu.2026.1761552</link>
        <title><![CDATA[Pregnane X receptor (NR1I2) deficiency in mice reveals context-dependent regulation of inflammatory homeostasis]]></title>
        <pubdate>2026-05-12T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Salah Edden Amini</author>
        <description><![CDATA[Nuclear receptor subfamily 1 group I member 2 (NR1I2; mouse ortholog Nr1i2), also known as the pregnane X receptor (PXR) or steroid and xenobiotic receptor (SXR), is a ligand-activated transcription factor classically known for its role in xenobiotic metabolism and detoxification. Beyond these canonical functions, accumulating evidence identifies NR1I2 as a key regulator of inflammation and intestinal homeostasis, particularly in inflammatory bowel disease (IBD), where dysregulated inflammatory responses are central to disease pathogenesis and NR1I2 expression is often reduced. In this review, we integrate data from whole-body and tissue-specific Nr1i2-deficient mouse models, as well as knockdown and ligand-based approaches, to define the role of Nr1i2 in intestinal inflammation under basal and pathological conditions. These studies collectively show that whole-body Nr1i2 deficiency disrupts intestinal homeostasis, impairs barrier integrity, and enhances innate immune activation, whereas tissue-restricted deletion, especially within the epithelium, frequently fails to reproduce these phenotypes, underscoring the importance of coordinated Nr1i2 activity across multiple cellular compartments. Across experimental models, most often Nr1i2 deficiency commonly exacerbates intestinal injury, particularly in response to microbial toxins or chemical damage, however attenuated inflammatory responses have been reported in selected metabolic or injury contexts. Conversely, pharmacological activation of Nr1i2 confers protective and restorative effects in a ligand-, tissue-, and context-dependent manner. Together, these findings establish NR1I2 not as a simple anti-inflammatory switch, but as an immune–metabolic integrator that coordinates xenobiotic detoxification, microbial-derived signal sensing, and restraint of innate inflammatory pathways. This review provides a conceptual framework for future studies aimed at elucidating the cell- and context-specific functions of NR1I2 and for guiding the development of targeted therapeutic strategies for intestinal inflammatory disorders.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fimmu.2026.1835853</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fimmu.2026.1835853</link>
        <title><![CDATA[Case Report: Cytokine storm syndrome causing retinal inflammatory factor storm]]></title>
        <pubdate>2026-05-12T00:00:00Z</pubdate>
        <category>Case Report</category>
        <author>Na Liu</author><author>Jingyi Bai</author><author>Gaixia Zhai</author><author>Shaopeng Wang</author>
        <description><![CDATA[Cytokine storm syndrome (CSS) represents a severe systemic inflammatory condition precipitated by the hyperactivation of immune cells and the consequent excessive release of cytokines, triggered by various factors. This report details the case of a 23-year-old woman admitted with acute high fever and subsequently referred to the ophthalmology department due to blurred vision. Multimodal imaging documented the progression of inflammatory cytokine storm in her fundus, and intraocular fluid analysis revealed abnormal cytokine levels. Following the resolution of inflammation, ocular symptoms and signs showed marked improvement. This report describes ocular manifestations of cytokine storm syndrome, underscoring the susceptibility of the fundus to systemic immune dysregulation despite the presence of the blood-retinal barrier.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fimmu.2026.1827640</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fimmu.2026.1827640</link>
        <title><![CDATA[Cisplatin - induced peripheral neuropathy and biomarkers of gut microbial translocation in testicular germ cell tumor survivors]]></title>
        <pubdate>2026-05-11T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Dominika Rychtarikova</author><author>Katarina Kalavska</author><author>Jana Obertova</author><author>Patrik Palacka</author><author>Katarina Rejlekova</author><author>Zuzana Sycova-Mila</author><author>Zuzana Orszaghova</author><author>Peter Lesko</author><author>Rateb Alzeer</author><author>Lucia Vasilkova</author><author>Daniela Svetlovska</author><author>Beata Mladosievicova</author><author>Michal Pastorek</author><author>Matej Rychtarik</author><author>Barbora Vlkova</author><author>Peter Celec</author><author>Michal Mego</author><author>Michal Chovanec</author>
        <description><![CDATA[BackgroundCisplatin-induced peripheral neuropathy (CIPN) is a frequent and often persistent complication in survivors of testicular germ cell tumors (GCT) treated with curative therapy. Although several mechanisms have been proposed, the biological drivers of long-term neurotoxicity remain incompletely understood. Disruption of intestinal barrier integrity during chemotherapy or radiotherapy may promote gut microbial translocation (GMT), leading to systemic immune activation and chronic inflammation that could contribute to neuropathy development. This study investigated the relationship between circulating biomarkers of GMT and symptoms of CIPN in long-term GCT survivors.MethodsA total of 170 GCT survivors (median age 41 years) from the National Cancer Institute of Slovakia were included, with a median follow-up of 10 years after treatment. Participants completed the EORTC QLQ-CIPN20 questionnaire assessing sensory, motor, and autonomic neuropathy. Peripheral blood samples were analyzed for plasma biomarkers associated with gut microbial translocation and innate immune activation, including soluble CD14 (sCD14), high-mobility group box-1 (HMGB1), lipopolysaccharide (LPS), and D-lactate. Associations between biomarker concentrations and CIPN scores were evaluated across treatment groups: orchiectomy only (active surveillance, n=28), cisplatin-based chemotherapy (n=119), radiotherapy (n=14), and combined chemoradiotherapy (n=9).ResultsPatients with higher plasma sCD14 levels had significantly higher overall CIPN scores (7.6% increase, p=0.019) and worse sensory function (9.5% increase, p=0.019) compared with those with lower levels. Patients treated with chemotherapy exhibited significantly higher plasma sCD14 levels than those under active surveillance (6613 vs. 3768 μg/L, p = 0.009). Among chemotherapy-treated patients, elevated sCD14 was associated with a higher risk of motor neuropathy (RR = 3.5, 95% CI 1.21–10.14, p=0.020). In survivors receiving combined chemotherapy and radiotherapy, increased sCD14 levels were associated with a higher risk of autonomic neuropathy (RR = 2.85, 95% CI 1.11–7.30, p=0.029). Elevated HMGB1 was also associated with an increased probability of autonomic dysfunction (RR = 2.15, 95% CI 1.07–4.33, p=0.015). No significant associations were observed between cumulative cisplatin dose and GMT biomarkers.ConclusionElevated biomarkers of gut microbial translocation, particularly sCD14, are associated with increased severity of CIPN in long-term GCT survivors. These findings support the hypothesis that treatment-related intestinal barrier disruption and subsequent immune activation may contribute to persistent neurotoxicity in cancer survivorship.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fimmu.2026.1746724</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fimmu.2026.1746724</link>
        <title><![CDATA[Elevated plasma cholesterol improves sepsis outcome by promoting hepatic metabolic reprogramming]]></title>
        <pubdate>2026-05-11T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Qian Wang</author><author>Jianyao Xue</author><author>Ling Guo</author><author>Dan Hao</author><author>Misa Ito</author><author>Rianna Reese</author><author>Bin Huang</author><author>Congqing Wu</author><author>Xiang-An Li</author>
        <description><![CDATA[BackgroundSepsis is a life-threatening condition with high mortality and limited therapeutic options. This study investigated the association between plasma cholesterol levels and sepsis survival and explored the mechanisms by which elevated cholesterol confers protection.MethodsWe analyzed 2,787 sepsis patients from the MIMIC-IV database, comparing cholesterol levels between 28-day survivors and non-survivors and assessing mortality risk using multivariable Cox regression. To test causality, C57BL/6J mice were fed either a high-cholesterol diet (HCD) or a regular diet (RD) before cecal ligation and puncture (CLP).ResultsSurvivors had significantly higher cholesterol than non-survivors (median 135 vs. 126 mg/dL; p < 0.001). High cholesterol (≥133 mg/dL) was independently associated with reduced 28-day mortality (adjusted HR = 0.80; 95% CI: 0.67–0.95; p = 0.012). In mice, HCD elevated plasma cholesterol and improved survival (52.5% to 90%), through a mechanism that is not primarily explained by broad immune activation. Hepatic transcriptomics revealed metabolic reprogramming, including enhanced oxidative phosphorylation and antioxidant pathways, with suppression of endoplasmic reticulum proteostasis. Inhibition of mitochondrial respiration abolished the survival benefit.ConclusionsElevated plasma cholesterol is associated with improved sepsis outcomes, likely through promoting hepatic metabolic reprogramming. Targeting hepatic bioenergetics is a potential therapeutic approach.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fimmu.2026.1832309</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fimmu.2026.1832309</link>
        <title><![CDATA[Lactylation-driven PDLIM1/PDAP1 axis remodels the inflammatory landscape of acute lung injury: mechanistic insights and precision intervention]]></title>
        <pubdate>2026-05-11T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Hexiao Tang</author><author>Congkuan Song</author><author>Guiomar Correia</author><author>Changsheng Li</author><author>Daoquan Liu</author><author>Xuefeng Zhou</author>
        <description><![CDATA[IntroductionAcute lung injury (ALI) remains a lethal clinical challenge driven by an uncontrolled “cytokine storm” resulting from dysregulated inflammatory networks. The metabolic and molecular mechanisms orchestrating this process remain incompletely understood.MethodsWe integrated multi-omics profiling with functional analyses in murine models and human iPSC-derived alveolar organoids. Key molecular players were identified through loss-of-function and pharmacological interventions, and the effects of a dual-target strategy using progesterone (PT) and ethyl methanesulfonate (EMS) were evaluated.ResultsMetabolic reprogramming-driven lactylation emerged as a central orchestrator of inflammatory progression. PDAP1 lactylation acts as a pivotal metabolic switch for NLRP3 inflammasome activation and selective IL-1β release. Functional deficiency of PDLIM1 releases the molecular brake on NF-κB signaling, precipitating a broad-spectrum inflammatory cascade. These modifications bridge metabolic stress with oxidative damage via the NRF2/GPX4-mediated ferroptotic pathway. The “dual-target, dual-drug” intervention—PT targeting the PDLIM1 axis and EMS selectively disrupting PDAP1-mediated IL-1β maturation—effectively quelled systemic inflammation and attenuated ALI pathology in both in vivo and organoid models.DiscussionThis study elucidates a novel metabolic-immune coupling mechanism in pulmonary polarization, shifting the focus from pan-inflammatory suppression toward precision immunomodulation. The findings provide a transformative theoretical paradigm for the management of ALI.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fimmu.2026.1831712</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fimmu.2026.1831712</link>
        <title><![CDATA[The host ubiquitination system dynamically regulates the inflammatory response of macrophages to bacteria]]></title>
        <pubdate>2026-05-11T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Jinru Liu</author><author>Xiaomei Li</author><author>Luna He</author><author>Xin Wang</author><author>Hongyuan Yang</author><author>Xianggui Yang</author><author>Jun Zeng</author>
        <description><![CDATA[Resistant bacterial infections have become a major global public health challenge, claiming millions of lives annually and imposing enormous economic burdens. The core issue lies in the imbalance of the host immune system, particularly macrophage function. This review elucidates the pivotal role of the host ubiquitin system in macrophage antimicrobial immunity. It systematically examines how this system leverages its unique enzyme-substrate network to orchestrate immune responses with dynamic equilibrium and precision, achieved through two critical pathways: the appropriate modulation of inflammatory signaling and the targeted clearance of intracellular pathogens. Within the Toll-like receptor (TLR)/Nuclear factor kappa-B (NF-κB) pathway, the ubiquitination system initiates inflammatory responses by activating molecules such as TRAF6, while undergoing negative feedback regulation via deubiquitinating enzymes like A20 to prevent excessive inflammatory damage. Within the autophagy pathway, ubiquitination functions as a “targeting system,” where ubiquitin ligases like Parkin and RNF213 mark and eliminate intracellular bacteria such as (Mtb) and Salmonella. In-depth analysis of the ubiquitin system’s specific roles in infection immunity and distinct bacterial infections holds significant importance for elucidating the molecular mechanisms underlying host-pathogen interactions. It will also provide key targets and novel perspectives for developing novel therapeutic strategies against drug-resistant bacterial infections.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fimmu.2026.1833346</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fimmu.2026.1833346</link>
        <title><![CDATA[Integrated transcriptomic and proteomic profiling implicates prostaglandin–nitric oxide network dysregulation in uterine microcirculatory impairment in primary dysmenorrhea]]></title>
        <pubdate>2026-05-11T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Yufei Li</author><author>Zongtong Yang</author><author>Beibei Yu</author><author>Xinjun Zhang</author><author>Xiaojing Li</author><author>Wenjing Chen</author><author>Mengyu Yuan</author><author>Zaiyun Sui</author><author>Yue Zhang</author><author>Wenjing Hou</author><author>Demin Gao</author>
        <description><![CDATA[BackgroundPrimary dysmenorrhea (PD) is a prevalent gynecological disorder characterized by severe menstrual pain. Although excessive prostaglandin activity is a recognized driver of uterine hypercontractility, the molecular mechanisms linking prostaglandin imbalance to nitric oxide (NO) deficiency, coagulation abnormalities, and impaired uterine microcirculation remain incompletely understood.MethodsA PD model was established in 12 female Sprague–Dawley rats (control, n = 6; PD, n = 6) using estradiol valerate, repeated cold exposure, and oxytocin stimulation. Behavioral testing, biochemical and hormonal assays, histopathological evaluation, coagulation analysis, uterine microcirculation assessment, integrated transcriptomic and proteomic analyses, and targeted measurement of arginine and proline were performed to characterize PD-associated alterations.ResultsPD rats exhibited marked hyperalgesia, uterine hypercontractility, and reduced uterine blood perfusion. These changes were accompanied by significantly elevated uterine PGF2α and PGE2 levels, together with an increased PGF2α/PGE2 ratio (P < 0.01), indicating a shift toward a contractile and vasoconstrictive prostaglandin profile. PD rats also showed decreased plasma NO and β-endorphin (β-EP) levels, altered estradiol (E2) and progesterone (P) levels, uterine histopathological injury, and coagulation disturbance, consistent with impaired vascular regulation and endogenous analgesic capacity. Integrated transcriptomic and proteomic analyses revealed widespread molecular dysregulation in PD, with arginine and proline metabolism identified as the only pathway significantly enriched at both levels. Consistently, targeted measurement confirmed elevated uterine arginine and proline levels, suggesting a potential impairment in arginine utilization that may contribute to reduced NO bioavailability.ConclusionThese findings support a systems-level model in which prostaglandin imbalance, coagulation-associated microcirculatory dysfunction, and dysregulated arginine–proline metabolism may jointly contribute to uterine ischemia and pain sensitization in PD. Our study proposes a refined molecular framework for PD pathogenesis and highlights the arginine–NO axis as a potential therapeutic target tworthy of future investigation.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fimmu.2026.1777938</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fimmu.2026.1777938</link>
        <title><![CDATA[Transcriptomic analysis reveals immune dysregulation and identifies key genes in ICU patients with severe ARDS]]></title>
        <pubdate>2026-05-11T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Haili Hu</author><author>Denghui Dou</author><author>Ruiling Shang</author><author>Rongzhi Luo</author>
        <description><![CDATA[ObjectiveAcute respiratory distress syndrome (ARDS) is characterized by severe immune dysregulation, yet its molecular determinants remain poorly defined. This study aimed to delineate the immune imbalance landscape of ICU patients with ARDS and to validate the expression and potential functional relevance of candidate hub genes through in vitro experiments.MethodsBulk transcriptomic datasets were merged and analyzed using differential expression, WGCNA, and machine learning approaches. Functional enrichment and cell deconvolution were assessed, followed by single-cell transcriptomic validation. In vitro experiments with LPS-induced THP-1 cells were performed to confirm candidate gene expression.ResultsCombined analyses highlighted immune-related pathways and revealed marked alterations in innate and adaptive immune subsets. Two histone-related genes, H2BC4 and H2BC12, emerged as candidate hub genes with preferential expression in myeloid populations and inducible upregulation under inflammatory stimulation.ConclusionThis study provides novel insights into ARDS immunopathogenesis and identifies potential molecular targets that may inform future diagnostic and therapeutic strategies.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fimmu.2026.1823993</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fimmu.2026.1823993</link>
        <title><![CDATA[Metabolism-driven emerging acylation modifications in COPD: from elucidation of fundamental mechanisms to clinical diagnosis and treatment]]></title>
        <pubdate>2026-05-11T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Guanglei Chen</author><author>Yunzhi Chen</author><author>Cancan Chu</author><author>Xing Zhu</author>
        <description><![CDATA[The progression of chronic obstructive pulmonary disease (COPD) is closely associated with metabolic reprogramming in pulmonary and immune cells. Under stresses such as cigarette smoke exposure, hypoxia, and infection, cells exhibit enhanced glycolysis, impaired mitochondrial oxidative metabolism, and altered tricarboxylic acid (TCA) cycle flux, resulting in abnormal accumulation of metabolites including lactate, succinate, and various acyl-coenzyme A species. These molecules, acting as acyl donors, drive emerging lysine acylation modifications (e.g., lactylation, succinylation, crotonylation), which play pivotal regulatory roles in airway inflammation, oxidative stress, and tissue remodeling by modulating chromatin states of histones or enzymatic activities of non-histone proteins. Studies have shown that histone lactylation (e.g., H3K14la, H4K12la) markedly induces senescence in pulmonary epithelial cells by activating p53 or CD38 expression and exacerbates pathological alterations, whereas succinylation and crotonylation show potential in regulating mitochondrial homeostasis and immune transcriptional programs. Non-histone acylation also plays an important role in feedback regulation of metabolic enzyme function and in proteostasis regulation. To achieve precision diagnosis and treatment, this review established an evidence-grading system based on strength of supporting evidence, indicating that high-strength sites such as lactylation should be prioritized for clinical translation. Future precision prevention and treatment of COPD should shift from mere description of modification abundance to causal validation of key sites, and should prioritize the development of smallmolecule drugs with isoform selectivity, in combination with pulmonary local delivery technologies to balance efficacy and safety. In addition, combined evaluation of specific metabolite levels and the acylation status of key proteins is expected to enable the development of biomarkers with greater predictive capacity, providing scientific support for molecular subtyping and precision intervention in COPD.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fimmu.2026.1831854</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fimmu.2026.1831854</link>
        <title><![CDATA[RORα: a critical nexus in the crosstalk between cholesterol metabolism and macrophage polarization]]></title>
        <pubdate>2026-05-08T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Dengju Li</author><author>Guangxian Liu</author><author>Xiangdong Wen</author><author>Guojiang Zhang</author><author>Kaixuan Liu</author><author>Lin Yuan</author><author>Bingbing Yu</author><author>Senbo An</author>
        <description><![CDATA[Retinoic acid receptor-related orphan receptor-α (RORα), a nuclear receptor transcription factor, is essential for maintaining organismal homeostasis and regulating diverse physio-pathological processes. However, its emerging role as a molecular nexus that integrates cholesterol metabolism with macrophage polarization to promote metabolic inflammation has not been systematically summarized. Cholesterol synthesis, transport, and efflux are critical for macrophage polarization. RORα regulates key components of these metabolic pathways and the associated transcriptional mechanisms driving polarization. Moreover, RORα regulates various other immune cells, such as T cells and microglia. This review aims to elucidate the core mechanisms of RORα in the crosstalk between cholesterol metabolism and inflammation, providing a novel method for therapeutic strategies.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fimmu.2026.1703552</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fimmu.2026.1703552</link>
        <title><![CDATA[Targeting T cell metabolism and polarization to modulate post-stroke immune responses and improve outcomes]]></title>
        <pubdate>2026-05-08T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Juliane Gellrich</author><author>Nora Bödecker</author><author>Imke Reich</author><author>Johanna Ruhnau</author><author>Stefan Groß</author><author>Susanne H. Kirsch</author><author>Rolf Müller</author><author>Juliane Schulze</author><author>Antje Vogelgesang</author>
        <description><![CDATA[BackgroundT cells drive post-stroke secondary brain injury, with the Th17/Treg balance shaping post-stroke inflammation. Soraphen A (SorA) inhibits Th17 polarization while preserving Tregs. We examined SorA’s effects on post-stroke T cell activation – distinguishing antigen-specific from bystander activation – including inflammatory conditions induced by LPS.MethodsMale Nur77GFP mice (12–14 weeks) underwent tMCAO. At reperfusion, mice received intraperitoneal LPS or vehicle; SorA or vehicle was given 2 h later and daily thereafter. MRI at 16 h and 7 d confirmed infarcts and measured lesion volumes. Functional outcomes were assessed by daily scoring and behavioral tests before surgery and at 2 and 6 d. T cell activation and polarization were analyzed by flow cytometry in brain, lungs, spleen, blood, and lymph nodes at 16 h, 2, 3, and 7 d, with GFP indicating antigen-specific activation.ResultsLPS worsened functional outcomes and increased peripheral T cell activation post-stroke. SorA improved functional recovery, reduced peripheral T cell activation and enhanced antigen-specific T cell activation. SorA increased Treg in LPS-treated mice and reversed LPS-induced alterations in both T cell activation and behavior.ConclusionsSoraphen A modulates systemic and organ-specific T cell responses in experimental ischemic stroke and improves outcomes. SorA increases regulatory T cells, reverses LPS-associated T cell activation (CD25, CD69, PD-1) and behavioral deficits, and shifts responses toward antigen-specific T cell receptor-mediated activation. These results support SorA as a promising immunomodulatory strategy to refine post-stroke immunity, extend the therapeutic window, and improve outcomes with potential benefits in the context of post-stroke infections.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fimmu.2026.1836038</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fimmu.2026.1836038</link>
        <title><![CDATA[Macrophage-derived CCL20–CCR6 signaling as a driver of immune recruitment in abdominal aortic aneurysm]]></title>
        <pubdate>2026-05-08T00:00:00Z</pubdate>
        <category>General Commentary</category>
        <author>Cheng Wang</author><author>Ling Ye</author>
        <description></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/fimmu.2026.1799968</guid>
        <link>https://www.frontiersin.org/articles/10.3389/fimmu.2026.1799968</link>
        <title><![CDATA[Serum and cerebrospinal fluid neuroinflammatory biomarkers and trimethylamine N-oxide: associations with white matter lesion severity]]></title>
        <pubdate>2026-05-08T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Xinxin Cheng</author><author>Changjiang Luo</author><author>Xudong Zhang</author><author>Huicong Xiao</author><author>Qi An</author><author>Chuanqiang Qu</author>
        <description><![CDATA[IntroductionThis study aimed to investigate the association between a multi-panel biomarker profile across the blood-brain barrier and the severity of white matter lesions (WML) in 42 patients [mean age: 60.3 ± 12.1 years; 45.2% male], suggesting a potential inflammatory endotype rather than defining a distinct phenotype due to the cross-sectional design and limited sample size. We assessed the gut-brain axis role in WML pathogenesis through analysis of paired serum and cerebrospinal fluid samples.MethodsIn this cross-sectional clinical study, 42 patients (aged 16–78 years; inclusion of younger subjects was based on radiological confirmation of WML unrelated to acute cerebrovascular events) with radiologically confirmed WML were stratified into four severity groups based on combined Fazekas global score (range 0–3, incorporating both periventricular and deep white matter hyperintensities). Levels of six biomarkers—interleukin-1β (IL-1β), matrix metalloproteinase-2 (MMP-2), tumor necrosis factor-α (TNF-α), trimethylamine N-oxide (TMAO), S100 calcium-binding protein β (S100β), and immunoglobulin G (IgG)—were simultaneously quantified in paired serum and cerebrospinal fluid (CSF) samples using ELISA. Statistical analyses included: (1) group comparisons using one-way ANOVA with LSD post-hoc tests; (2) Spearman correlation analyses; (3) multivariable ordinal logistic regression adjusting for age, sex, hypertension, diabetes, and BMI to control confounding; (4) False Discovery Rate (FDR) correction for multiple comparisons (Benjamini-Hochberg method). Post-hoc power analysis and effect sizes (η², Cohen’s d) were reported.ResultsSeverity-dependent increases in IL-1β, TNF-α, and the gut-derived metabolite TMAO were observed in both serum and CSF. After adjustment for confounders, CSF TNF-α (adjusted OR = 1.95, 95% CI: 1.42–2.68, P<0.001) and serum MMP-2 (adjusted OR = 1.72, 95% CI: 1.28–2.31, P<0.001) demonstrated the strongest correlations with WML severity among all biomarkers, establishing them as primary candidate biomarkers. An inverse concentration pattern (elevated serum/decreased CSF) was observed for MMP-2, suggesting stage-specific roles in blood-brain barrier dynamics. CSF S100β levels increased with severity (r=0.487, P<0.001), consistent with parenchymal injury. Regarding IgG, while univariate analysis showed marginal significance in CSF (P = 0.045), FDR correction rendered this non-significant (q=0.12), and no significant correlation was found with Fazekas grade (P = 0.068), suggesting limited association with WML severity in this cohort.ConclusionThis study suggests a potential neuroinflammatory profile in WML, characterized by coupled peripheral and central inflammation associated with gut-derived TMAO, though causality cannot be inferred from this cross-sectional design. CSF TNF-α and serum MMP-2 are proposed as precision biomarkers for stratifying WML severity. These findings should be interpreted as a hypothesis-generating framework integrating dysregulated gut-brain axis signaling, central cytokine surges, and blood-brain barrier disruption into a unified pathogenic cascade, providing mechanistic insights for targeted anti-inflammatory strategies in cerebrovascular disease. However, the clinical applicability requires further validation given the invasive nature of CSF collection.]]></description>
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