description
Interleukin (IL)-17-producing helper T (Th17) cells serve as a subset of CD4+ T cells involved in epithelial cell- and neutrophil mediated immune responses against extracellular microbes and in the pathogenesis of autoimmune diseases. In vivo, Th17 differentiation requires antigen presentation and co-stimulation, and activation of antigen presenting-cells (APCs) to produce TGF-beta, IL-6, IL-1, IL-23 and IL-21. This initial activation results in the activation and up-regulation of STAT3, ROR(gamma)t and other transcriptional factors in CD4+ T cells, which bind to the promoter regions of the IL-17, IL-21 and IL-22 genes and induce IL-17, IL-21 and IL-22. In contrast, the differentiation of Th17 cells and their IL-17 expression are negatively regulated by IL-2, Th2 cytokine IL-4, IL-27 and Th1 cytokine IFN-gamma through STAT5, STAT6 and STAT1 activation, respectively. Retinoid acid and the combination of IL-2 and TGF-beta upregulate Foxp3, which also downregulates cytokines like IL-17 and IL-21. The inhibition of Th17 differentiation may serve as a protective strategy to 'fine-tune' the expression IL-17 so it does not cause excessive inflammation. Thus, balanced differentiation of Th cells is crucial for immunity and host protection

external resources
NCBI:1469482
KEGG:hsa04659
PUBMED:23325835
PUBMED:23036716
PUBMED:20488727
PUBMED:21151104
PUBMED:21084214
PUBMED:20054607
PUBMED:22754770
PUBMED:22640807
PUBMED:19379825
PUBMED:22133865
PUBMED:22324470
PUBMED:17768419
PUBMED:18408735
PUBMED:21776333
PUBMED:26253381
PUBMED:16200068
PUBMED:18362914
PUBMED:24325586
PUBMED:19381306
PUBMED:18166487

genes
AHR , RUNX1 , CD3D , CD3E , CD3G , CD247 , CD4 , CHUK , MAPK14 , FOS , MTOR , GATA3 , HIF1A , HLA-DMA , HLA-DMB , HLA-DOA , HLA-DOB , HLA-DPA1 , HLA-DPB1 , HLA-DQA1 , HLA-DQA2 , HLA-DQB1 , HLA-DRA , HLA-DRB1 , HLA-DRB5 , HSP90AA1 , HSP90AB1 , IFNG , IFNGR1 , IFNGR2 , IKBKB , IL1B , IL1R1 , IL1RAP , IL2 , IL2RA , IL2RB , IL2RG , IL4 , IL4R , IL6 , IL6R , IL6ST , IL12RB1 , IL17A , IRF4 , JAK1 , JAK2 , JAK3 , JUN , LCK , SMAD2 , SMAD3 , SMAD4 , NFATC1 , NFATC2 , NFATC3 , NFKB1 , NFKBIA , NFKBIB , NFKBIE , PLCG1 , PPP3CA , PPP3CB , PPP3CC , PPP3R1 , PPP3R2 , PRKCQ , MAPK1 , MAPK3 , MAPK8 , MAPK11 , MAPK9 , MAPK10 , MAPK13 , RARA , RELA , RORA , RORC , RXRA , RXRB , RXRG , MAPK12 , STAT1 , STAT3 , STAT5A , STAT5B , STAT6 , TGFB1 , TGFBR1 , TGFBR2 , TYK2 , ZAP70 , IKBKG , IL27RA , LAT , TBX21 , IL21R , IL22 , FOXP3 , IL23A , IL17D , IL21 , IL17F , IL23R ,