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Differentiation of Th17 Subset Stimulated by zymosan, fungus, myobacteria Important cytokines for the Th17 differentiation Important transcription factors (TF) for the Th17 differentiation IL-6 TGF-? IL-23 IL-21 ROR-?t: master regulator ROR- ? STAT3 AhR Th17 and AhR The role of AhR in Th17 development and effector function revealed an environmental effect on Th17 generation. Veldhoen et al. The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins. Nature 453, 106–109 (2008). Quintana et al. Control of Treg and TH17 cell differentiation by the aryl hydrocarbon receptor. Nature 453, 65–71 (2008). Kimura et al. Aryl hydrocarbon receptor regulates Stat1 activation and participates in the development of Th17 cells. Proc. Natl. Acad. Sci. USA 105, 9721–9726 (2008). Veldhoen, et al. Natural agonists for aryl hydrocarbon receptor in culture medium are essential for optimal differentiation of Th17 T cells. J Exp Med, 2009 IMDM is better than 1640 for Th17 in vitro differentiation The differentiation of Th17 Subset CD4+CD25+ Regulatory T cells (Treg cells) A subset of CD4+ CD25+ T cells expressing Foxp3 Naturally present in immune system, constitute 5-10% of peripheral CD4+ T cells Suppress immune responses and maintain self-tolerance Sakaguchi et al. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol 1995 Hori et al. Control of regulatory T cell development by the transcription factor Foxp3. Science 2003 Fontenot et al. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nature Immunol 2003 Landmark papers about Treg Natural Treg cells (nTreg) thymic derived, highly controlled by thymic microenvironment Induced Treg cells (iTreg) peripherally generated Subsets of Treg cells TCR Co-stimulation C