"T helper 17 cells (Th17) are a newly discovered subset of T helper cells producing interleukin 17 (IL-17). They are considered developmentally distinct from Th1 and Th2 cells and excessive amounts of the cell are thought to play a key role in autoimmune disease such as multiple sclerosis (which was previously thought to be caused by Th1 cells), but also psoriasis, autoimmune uveitis, juvenile diabetes, rheumatoid arthritis, and Crohn's disease.
More specifically, they are thought to play a role in inflammation and tissue injury in these conditions. Th17 cells can cause severe autoimmune diseases, however they serve a very important function in anti-microbial immunity at epithelial /mucosal barriers. They produce cytokines (such as interleukin 22) which stimulates epithelial cells to produce anti-microbial proteins to clear out certain types of microbe (such as Candida and Staphylococcus). Thus, a severe lack of Th17 cells may leave the host susceptible to opportunistic infections."
"Autoimmune diseases in the TH17 era" in Braz J Med Biol Res (2009)
"A new subtype of CD4+ T lymphocytes characterized by the production of interleukin 17, i.e., TH17 cells, has been recently described. This novel T cell subset is distinct from type 1 and type 2 T helper cells. The major feature of this subpopulation is to generate significant amounts of pro-inflammatory cytokines, therefore appearing to be critically involved in protection against infection caused by extracellular microorganisms, and in the pathogenesis of autoimmune diseases and allergy. The dynamic balance among subsets of T cells is important for the modulation of several steps of the immune response. Disturbances in this balance may cause a shift from normal immunologic physiology to the development of immune-mediated disorders. In autoimmune diseases, the fine balance between the proportion and degree of activation of the various T lymphocyte subsets can contribute to persistent undesirable inflammatory responses and tissue replacement by fibrosis. This review highlights the importance of TH17 cells in this process by providing an update on the biology of these cells and focusing on their biology and differentiation processes in the context of immune-mediated chronic inflammatory diseases."
"Phenotypic and functional features of human Th17 cells" in J Exp Med (2007)
"T helper (Th) 17 cells represent a novel subset of CD4+ T cells that are protective against extracellular microbes, but are responsible for autoimmune disorders in mice. However, their properties in humans are only partially known. We demonstrate the presence of Th17 cells, some of which produce both interleukin (IL)-17 and interferon (IFN)-γ (Th17/Th1), in the gut of patients with Crohn's disease. Both Th17 and Th17/Th1 clones showed selective expression of IL-23R, CCR6, and the transcription factor RORγt, and they exhibited similar functional features, such as the ability to help B cells, low cytotoxicity, and poor susceptibility to regulation by autologous regulatory T cells. Interestingly, these subsets also expressed the Th1-transcription factor T-bet, and stimulation of these cells in the presence of IL-12 down-regulated the expression of RORγt and the production of IL-17, but induced IFN-γ. These effects were partially inhibited in presence of IL-23. Similar receptor expression and functional capabilities were observed in freshly derived IL-17–producing peripheral blood and tonsillar CD4+ T cells. The demonstration of selective markers for human Th17 cells may help us to understand their pathogenic role. Moreover, the identification of a subset of cells sharing features of both Th1 and Th17, which can arise from the modulation of Th17 cells by IL-12, may raise new issues concerning developmental and/or functional relationships between Th17 and Th1."
"Crohn’s disease: Th1, Th17 or both? The change of a paradigm: new immunological and genetic insights implicate Th17 cells in the pathogenesis of Crohn’s disease" in Gut (2009)
"Traditionally, Crohn’s disease has been associated with a Th1 cytokine profile, while Th2 cytokines are modulators of ulcerative colitis. This concept has been challenged by the description of tolerising regulatory T cells (Treg) and by proinflammatory Th17 cells, a novel T cell population characterised by the master transcription factor RORγt, the surface markers IL23R and CCR6, and by production of the proinflammatory cytokines IL17A, IL17F, IL21, IL22 and IL26, and the chemokine CCL20. Th17 cells differentiate under the influence of IL1β, IL6, IL21 and IL23. Recent studies indicate that TGFβ is essential not only for the development of murine Th17 cells but also for differentiation of human Th17 cells. TGFβ reciprocally regulates the differentiation of inflammatory Th17 cells and suppressive Treg subsets, with the concomitant presence of proinflammatory cytokines favouring Th17 cell differentiation. Several studies demonstrated an important role of Th17 cells in intestinal inflammation, particularly in Crohn’s disease. Genome-wide association studies indicate that are associated with susceptibility to Crohn’s disease and partly also to ulcerative colitis. Taken together, both Th1 and Th17 cells are important mediators of inflammation in Crohn’s disease, although activities previously ascribed to IL12 may be mediated by IL23. Anti-IL12/IL23p40 antibody therapy, which targets both Th1 and Th17 cells, is effective in Crohn’s disease. However, the complex relationship between Th1 and Th17 cells has not been completely analysed. This will be of great importance to delineate the specific contributions of these cells to Crohn’s disease and other autoimmune diseases."
"Th1/Th17 Immune Response Is Induced by Mesenteric Lymph Node Dendritic Cells in Crohn's Disease" in Gastroenterology (2008)
"Conclusions: Our findings revealed that mesenteric lymph node is the key pathogenic location of CD elicited by the unique cytokine milieu produced by DCs leading to a dysregulated Th1/Th17 immune response."
"Intestinal homeostasis and its breakdown in inflammatory bowel disease" in Nature (2011)
"The relative enrichment of TH17 cells at mucosal sites, together with the increased levels of TH17 cytokines in the inflamed gut, has fuelled interest in their potential role in IBD pathogenesis36, 39. TH17 cells produce several cytokines, including IL-17A, IL-17F, IL-21 and IL-22 (ref. 36)."
"The Role of Th17 in Neuroimmune Disorders: A Target for CAM Therapy. Part III" in Evidence-Based Complementary and Alternative Medicine (2011)
"Thus, based on the best available evidence, the modification of TH-lineage requires a full understanding of the neuroimmune inflammatory pathway, which is necessary to combat inflammation, autoimmunity and neurodegeneration. In this regard it is vital to understand the significant roles played in neuroinflammation by Th17 and its effector cytokine, IL-17, in conjunction with IL-23, IL-27 and Th1 autoreactive cells."
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