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Th17 Cells

T helper type 17 (Th17) cells are involved in the immune response mounted against specific fungi and extracellular bacteria. In mice, Th17 cells develop from naive CD4+ T cells in the presence of TGF-beta and IL-6. These cytokines induce the STAT3-dependent expression of IL-21, IL-23 R, and the transcription factor, ROR gamma t. IL-21 and IL-23 regulate the establishment and clonal expansion of Th17 cells, while ROR gamma t-induced gene expression leads to the secretion of IL-17A, IL-17F, and IL-22. Cytokines secreted by Th17 cells stimulate chemokine secretion by resident cells, leading to the recruitment of neutrophils and macrophages to sites of inflammation. These cells, in turn, produce additional cytokines and proteases that further exacerbate the immune response. In contrast to mouse Th17 differentiation, Th17 polarization in humans requires IL-1 beta, IL-6, IL-21, and IL-23, but seems to be less dependent upon TGF-beta. One other notable difference is that human Th17 cells secrete IL-26, an IL-10 family cytokine without a murine homologue. Cytokines produced by Th17 cells can have both beneficial and pathogenic effects. While they play a central role in eliminating harmful microbes, persistent secretion of Th17 cytokines promotes chronic inflammation and may be involved in the pathogenesis of inflammatory and autoimmune diseases, including rheumatoid arthritis, multiple sclerosis, and inflammatory bowel disorders.