The gastrointestinal tract plays a central role in immune system, being able to mount efficient immune responses against pathogens, keeping the homeostasis of the human gut. However, conditions like Crohn’s disease (CD) or ulcerative colitis (UC), the main forms of inflammatory bowel diseases (IBD), are related to an excessive and uncontrolled immune response against normal microbiota, through the activation of CD4+ T helper (Th) cells. Classically, IBD was thought to be primarily mediated by Th1 cells in CD or Th2 cells in UC, but it is now known that Th17 cells and their related cytokines are crucial mediators in both conditions. Th17 cells massively infiltrate the inflamed intestine of IBD patients, where they produce interleukin- (IL-) 17A and other cytokines, triggering and amplifying the inflammatory process. However, these cells show functional plasticity, and they can be converted into either IFN-γ producing Th1 cells or regulatory T cells. This review will summarize the current knowledge regarding the regulation and functional role of Th17 cells in the gut. Deeper insights into their plasticity in inflammatory conditions will contribute to advancing our understanding of the mechanisms that regulate mucosal homeostasis and inflammation in the gut, promoting the design of novel therapeutic approaches for IBD. 1. Introduction Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder of the gastrointestinal tract that comprises two major conditions: Crohn’s disease (CD) and ulcerative colitis (UC). These pathologies are characterized by abdominal pain, fever, chronic diarrhea, and rectal bleeding due to ulceration of the inner lining of the colon and/or rectum, which can be accompanied by complications such as fistulation, stenosis, and abscesses in CD and megacolon in UC. Acute flares severely impair patient’s ability to lead a normal life, frequently requiring hospitalization and surgery, and may even be life threatening. At present, the pathogenesis of IBD remains elusive; however, the altered and chronic activation of the immune and inflammatory cascade in genetically susceptible individuals against unknown components of the luminal microflora seems to play a key role [1, 2] (Figure 1). The intestinal immune system is the largest and most complex component of the immune system in the human being. As the intestine comprises the major single epithelial interface in the body, which is populated by the greatest number and diversity of resident microbes, the intestinal immune system encounters therefore more antigens than any
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