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
,