Core Viewpoint - The article discusses the increasing prevalence of Inflammatory Bowel Disease (IBD) in China, highlighting the role of the IL17REL gene in the disease's susceptibility and its potential as a therapeutic target [2][8]. Group 1: Overview of IBD - IBD includes Ulcerative Colitis (UC) and Crohn's Disease (CD), characterized by chronic, non-specific intestinal inflammation with no known cure, lifelong recurrence, and potential disability [2]. - The incidence of IBD in China has been rising annually, with current treatments focusing on immunomodulators and corticosteroids to alleviate inflammation or surgical removal of affected gastrointestinal sections [2]. Group 2: IL17REL Gene Research - The IL17REL gene locus has been identified as associated with susceptibility to IBD, but its functional protein coding and causal contribution to disease mechanisms remain unclear [3]. - A study published in Nature Immunology reveals that IL-17REL plays a significant protective role in IBD by acting as a decoy receptor for IL-17 family cytokines, inhibiting the activation of the IL-17 signaling pathway and downstream inflammatory gene expression [4][7]. Group 3: Mechanism and Implications - The study confirms that the wild-type IL-17REL protein can bind to IL-17 cytokines and suppress intestinal inflammation, while IBD-related mutations in IL17REL lack this function [7][9]. - TGFβ1 induces IL17REL transcription, and its expression correlates positively with TGFB1 levels in IBD patients [7]. - In mouse models, the introduction of the IL17REL gene alleviates colitis induced by 2,4,6-trinitrobenzenesulfonic acid, whereas the introduction of IBD-related IL17REL mutations does not yield this effect [7]. - Therapeutic administration of IL-17REL protein can reduce colitis symptoms, indicating its potential as a treatment target for IBD [8].