The intestinal immune system is vital for maintaining mucosal homeostasis and mediating interactions between the host and its microbiota, thereby protecting against pathogenic threats. As the largest and most complex immune organ, it integrates various signals from dietary components, microbiota, epithelial cells, and immune networks to balance immune tolerance with activation. Disruption of this delicate balance is a prominent feature in multiple inflammatory gut disorders, such as inflammatory bowel disease (IBD), necrotizing enterocolitis (NEC), microscopic colitis, and systemic autoimmune conditions affecting the intestine. Despite recent advances in understanding its cellular and molecular architecture, there remain unanswered questions regarding the mechanisms underpinning these diseases and limitations in current therapeutic strategies.

Significant progress over recent decades has enhanced our comprehension of inflammatory gut diseases, specifically IBD, including Crohn's and ulcerative colitis, highlighting roles for innate and adaptive immune responses, epithelial barrier dysfunction, cytokine signaling, and microbial dysbiosis. However, persistent gaps in mechanistic knowledge and insufficient therapeutic efficacy, which fail to achieve long-term remission for all patients, denote ongoing challenges in the field. Addressing these knowledge gaps through innovative research strategies is crucial to developing effective interventions.

This Research Topic aims to illuminate recent advancements and novel concepts related to the intestinal immune system's dysregulation in inflammatory gut disorders. By fostering contributions from immunology, microbiology, gastroenterology, and translational medicine, we seek to deliver a comprehensive and cross-disciplinary study of mucosal immunology, providing insights into health and disease. To expand our understanding and improve patient outcomes, key areas of focus include elucidating early immune events that trigger chronic intestinal inflammation, identifying biomarkers predictive of disease progression and therapeutic response, and developing novel immune-modulatory strategies. Emphasis is given to leveraging cutting-edge technologies such as single-cell analyses, spatial transcriptomics, organoid models, and microbiome-based interventions, which hold promise for transforming gut immunology research and advancing precision medicine.

To gather further insights into the complexities of intestinal immune regulation, we welcome articles addressing, but not limited to, the following themes:

-Innate and adaptive immune mechanisms underpinning intestinal homeostasis and inflammation.
-Interactions between gut epithelium, microbiota, and immune cells in inflammatory disorders.
-Insights into immune cell plasticity and cytokine networks in the intestinal mucosa.
-Immunogenetics and environmental triggers of gut immune dysregulation.
-Microbiota-influenced modulation of mucosal immunity and its health/disease impact.
-Mechanisms driving action and resistance to immunotherapies in intestinal diseases.
-Development of immune-based biomarkers for diagnosis, stratification, and prognosis.
-Innovative therapeutic approaches targeting mucosal immune pathways.

This platform aims to consolidate findings, stimulate interdisciplinary dialogue, and drive the development of innovative immunological approaches for restoring intestinal immune balance and improving outcomes in patients with inflammatory gut disorders.

Lei Huang serves as a paid consultant for Oversea Business. All the other topic editors declare no conflicts of interest

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Innovations in targeting intestinal immunity for chronic inflammatory disorders