Inflammatory bowel disease (IBD) is a general term for both Crohn's disease and ulcerative colitis. It is a type of disease of chronic inflammation occurs in the gastrointestinal tract, and prolonged inflammation can cause damage to the gastrointestinal tract. In recent decades, the incidence of IBD has increased rapidly, and it’s estimated that 5 million people live with IBD in the world. Inflammatory bowel disease is a primary immunodeficiency disease caused by incompatibility or innate immune response or intestinal mucosal barrier defects in the human intestinal flora. It can cause the body to produce loose stools, diarrhea, severe colitis with deep ulcers and granulomas, weight loss and related growth restriction, and may even cause perianal disease, dermatological abnormalities, autoimmunity and increase the risk of some tumors. The prevalence of inflammatory bowel disease caused by mutations in the genes of IL10, IL10RA, IL10RB and FOXP3 is 100% or almost 100%, while pathogenic variants in XIAP such as any of the CGD genes and MVK show incomplete penetrance of inflammatory bowel disease.
IL10 acts as a key cytokine molecule that regulates intestinal mucosal homeostasis. Mutations in IL10 are associated with the risk of developing IBD. IL10 and its receptors co-regulate intestinal mucosal immune responses in vivo and mutations in the IL-10 receptor subunit proteins IL10RA and IL10RB are associated with IBD. It's reported that some structural changes in IL10RA may interfere with its binding affinity to IL10, thereby inhibiting IL10-induced IL10RA phosphorylation, ultimately impairing STAT3 activation and inhibiting inflammatory responses. CD4+ CD25+T regulatory cells (Tregs) have the effect of maintaining self-tolerance and preventing autoimmune diseases. IL-10 signaling in monocyte-derived dendritic cells regulates IFNγ secretion by CD4+ T cells. Lack of IL-10 signaling significantly increases IL-1β release from monocyte-derived dendritic cell(moDC), while IL-1β directly or indirectly enhances IFNγ secretion from CD4+ T cells by stimulating moDCs to secrete IL-12. FOXP3 is a member of the transcription factor expressed by CD4+CD25+T cells and is a symbol of transcriptional activity expression. Mutations in the FOXP3 gene can cause IBD. XIAP plays an important role in the key pathways of susceptibility to intestinal immunity and IBD, and it has a transduction effect in the nucleotide binding and oligomerization domain (NOD)-2 pathway. XIAP is linked to RIP2 by interaction with the NOD2 receptor, which causes Lys63-linked RIP2 polyubiquitination and is capable of recruiting LUBAC. The recruitment of LUBAC can trigger the production of ubiquitination in the body. Ubiquitination reaction leads to an increase in the production of cytokines, chemokines and antimicrobial peptides required for intestinal immunity, leading to the IBD.
To provide comprehensive consequences of these mutations of IL10, FOXP3 and other related genes, our platform offers the target DNA sequencing service and a custom inflammatory bowel disease panel, which can help researchers better understand the pathogenesis of IBD.
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