Editorial: Immune Responses at Barrier Tissues: Insights from Synthetic Biology in Therapeutics, Diagnostics, Mechanisms, and Beyond

Kong Chen^1*Siheng Chao¹Naoki Iwanaga²Hernan Felipe Peñaloza³Nicola Ivan Lorè¹

• ¹University of Pittsburgh, Pittsburgh, United States
• ²Nagasaki University Hospital, Nagasaki, Japan
• ³Millennium Institute on Immunology and Immunotherapy, Santiago, Chile

Infectious; IRCCS Ospedale San Raffaele, Milan, Italy.Barrier tissues separate the external environment from the internal environment of the human body. These specialized structures serve not only as passive physical barriers but also as dynamic regulators of molecular and cellular traffic, thereby playing a critical role in maintaining physiological homeostasis. Barrier integrity is essential across multiple systems, including the respiratory, urinary, gastrointestinal, and sensory systems. In pathological states, disruption of barrier function permits the translocation of inappropriate or excessive molecular species, which can precipitate aberrant immune activation, often skewed toward pro-inflammatory responses. Such immune dysregulation may exacerbate existing pathology or contribute to the onset of comorbid conditions.This research topic sheds light on the pathophysiology of barrier tissues is disease contexts across multiple organ systems. It emphasizes the underlying mechanisms of barrier tissue dysfunction and the immune system's role in these processes, while highlighting potential biological models and outlining future clinical research directions to manage diseases with barrier tissues in mind.The mini review by Simalee et al. describes the pathogenic roles and effects of inflammatory eosinophils (iEOS) and tissue resident eosinophils (rEOS) in Chronic rhinosinusitis with nasal polyps (CRSwNP). Simalee et al. discussed different populations of eosinophils and how an imbalance of iEOS and rEOS exacerbates the type 2 endotype of CRSwNP, both due to eosinophil mechanisms and by signaling to other immune cells. The authors also placed a heavy focus on the potential impact of CRSwNP treatments which further exploration of eosinophil population may offer; this includes anti-eosinophilia drug treatment or combinations and using subtypes of eosinophils as biomarkers in clinical disease management and as predictor variables in models.In their perspective article, Jin et al. explore the role of circulating immune complexes in the development of arthritis among patients with inflammatory bowel disease (IBD).They highlight how increased intestinal permeability, or "leaky gut", in IBD allows microbial products to enter the circulation. This translocation facilitates the formation and systemic distribution of immune complexes, which may deposit in joints and trigger inflammatory responses. The authors further discuss potential strategies to restore gut barrier integrity, emphasizing the therapeutic potential of butyrate, a short-chain fatty acid known to support epithelial health and reduce permeability. This work underscores the gut-joint axis as a possible target for preventing extraintestinal complications of IBD.The PrEP-treated and control groups, suggesting that oral PrEP does not compromise the mucosal epithelial barrier. Additionally, while TJ genes correlated with cytokine signaling, PrEP had no significant impact on inflammatory gene expression. These findings support the safety of oral PrEP in preserving epithelial integrity and encourage further investigation into its broader biological effects.In conclusion, this research topic highlights recent advancements in the study of barrier tissues across multiple organ systems. This topic presents clinically relevant discussions and insights into how dysfunctional barrier tissues may participate with health disorders. This topic aims to encourage further studies on barrier tissues and translational research, showcasing innovative models for studying barrier function, progress in biomarker discovery, and the development of novel diagnostic and treatment strategies.