Plasticity and Heterogeneity of TH17 Cells
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CitationSingaraju, Anvita. 2019. Plasticity and Heterogeneity of TH17 Cells. Master's thesis, Harvard Medical School.
AbstractAt homeostasis TH17 cells are most abundant in the lamina propria by accounting for 30-40% of all CD4+ memory T cells. Here, they play an important role in maintaining the intestinal integrity against the symbiont microbes with the production of IL-17A, IL-17F, IL-21 and IL-22. Interestingly, TH17 cells have been implicated in driving several autoimmune diseases including multiple sclerosis and inflammatory bowel diseases. The cells driving autoimmune disease are highly proinflammatory co-producing large amounts of IL-17A and interferon gamma. Several reports highlight the plastic nature of TH17 cells that vary depending on the immune environment they are present in. During autoimmune inflammation of the central nervous system, TH17 cells are known to differentiate into TH1 like cells and during the resolution, transition into T-regulatory and TR1- like cells. In this thesis we sought to identify factors that influence plasticity of non-pathogenic and pathogenic TH17 cells by establishing an in vitro system of TH17 trans-differentiation. We looked for similar differences in vivo using an IL-17A fate reporter model. Using this system, we could differentiate and analyze the heterogeneity of TH17 cells during homeostasis.
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