Entry Name Th17 cell differentiation - Myotis brandtii (Brandt's bat)
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.
Class Organismal Systems; Immune systemBRITE hierarchy
Pathway map Ortholog table Other DBs Organism Myotis brandtii (Brandt's bat) [GN:
myb ]
Gene 102239853 STAT3; signal transducer and activator of transcription 3 [KO:K04692 ]
102263971 HSP90AA1; heat shock protein 90 alpha family class A member 1 [KO:K04079 ]
102261247 HSP90AB1; heat shock protein 90 alpha family class B member 1 [KO:K04079 ]
102252603 HLA class II histocompatibility antigen, DP beta 1 chain [KO:K06752 ]
102242640 H-2 class II histocompatibility antigen, E-S beta chain [KO:K06752 ]
102241033 DLA class II histocompatibility antigen, DR-1 beta chain [KO:K06752 ]
102241645 DLA class II histocompatibility antigen, DR-1 beta chain [KO:K06752 ]
102242559 HLA class II histocompatibility antigen, DRB1-1 beta chain [KO:K06752 ]
102242249 HLA class II histocompatibility antigen, DRB1-4 beta chain [KO:K06752 ]
102263678 HLA class II histocompatibility antigen, DQ beta 1 chain [KO:K06752 ]
102255852 SLA class II histocompatibility antigen, DQ haplotype D alpha chain [KO:K06752 ]
102256158 HLA class II histocompatibility antigen, DQ beta 1 chain [KO:K06752 ]
102251097 SLA class II histocompatibility antigen, DQ haplotype D alpha chain [KO:K06752 ]
102250801 HLA class II histocompatibility antigen, DQ beta 1 chain [KO:K06752 ]
102242568 SLA class II histocompatibility antigen, DQ haplotype D beta chain [KO:K06752 ]
102242876 HLA class II histocompatibility antigen, DQ alpha 2 chain [KO:K06752 ]
102259226 boLa class II histocompatibility antigen, DQB*0101 beta chain-like [KO:K06752 ]
102249039 H-2 class II histocompatibility antigen, A-U alpha chain [KO:K06752 ]
102263829 HLA class II histocompatibility antigen, DR alpha chain [KO:K06752 ]
102245034 DLA class II histocompatibility antigen, DR-1 beta chain [KO:K06752 ]
102259410 HLA class II histocompatibility antigen, DRB1-4 beta chain-like [KO:K06752 ]
102249578 boLa class II histocompatibility antigen, DQB*0101 beta chain [KO:K06752 ]
102252319 RLA class II histocompatibility antigen, DP alpha-1 chain-like [KO:K06752 ]
102251129 HLA class II histocompatibility antigen, DQ alpha 2 chain [KO:K06752 ]
102251414 SLA class II histocompatibility antigen, DQ haplotype C beta chain-like [KO:K06752 ]
102244632 SLA class II histocompatibility antigen, DQ haplotype C beta chain-like [KO:K06752 ]
102245825 HLA class II histocompatibility antigen, DM beta chain [KO:K06752 ]
102246131 HLA class II histocompatibility antigen, DM alpha chain [KO:K06752 ]
102250711 PPP3R1; protein phosphatase 3 regulatory subunit B, alpha [KO:K06268 ]
102247129 PPP3R2; protein phosphatase 3 regulatory subunit B, beta [KO:K06268 ]
102252013 IKBKG; inhibitor of nuclear factor kappa B kinase subunit gamma [KO:K07210 ]
102246307 FOS; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379 ]
102260808 JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448 ]
102251654 STAT6; signal transducer and activator of transcription 6 [KO:K11225 ]
102243651 STAT1; signal transducer and activator of transcription 1 [KO:K11220 ]
102240764 STAT5A; signal transducer and activator of transcription 5A [KO:K11223 ]
102241062 STAT5B; signal transducer and activator of transcription 5B [KO:K11224 ]
Compound C01245 D-myo-Inositol 1,4,5-trisphosphate
Reference Authors Muranski P, Restifo NP
Title Essentials of Th17 cell commitment and plasticity.
Journal Reference Authors O'Shea JJ, Steward-Tharp SM, Laurence A, Watford WT, Wei L, Adamson AS, Fan S
Title Signal transduction and Th17 cell differentiation.
Journal Reference Authors Hirahara K, Ghoreschi K, Laurence A, Yang XP, Kanno Y, O'Shea JJ
Title Signal transduction pathways and transcriptional regulation in Th17 cell differentiation.
Journal Reference Authors Chen Z, Laurence A, O'Shea JJ
Title Signal transduction pathways and transcriptional regulation in the control of Th17 differentiation.
Journal Reference Authors Maddur MS, Miossec P, Kaveri SV, Bayry J
Title Th17 cells: biology, pathogenesis of autoimmune and inflammatory diseases, and therapeutic strategies.
Journal Reference Authors Hemdan NY, Birkenmeier G, Wichmann G
Title Key molecules in the differentiation and commitment program of T helper 17 (Th17) cells up-to-date.
Journal Reference Authors Dong C
Title TH17 cells in development: an updated view of their molecular identity and genetic programming.
Journal Reference Authors Torchinsky MB, Blander JM
Title T helper 17 cells: discovery, function, and physiological trigger.
Journal Reference Authors Jetten AM
Title Retinoid-related orphan receptors (RORs): critical roles in development, immunity, circadian rhythm, and cellular metabolism.
Journal Reference Authors Oestreich KJ, Weinmann AS
Title T-bet employs diverse regulatory mechanisms to repress transcription.
Journal Reference Authors Manni ML, Robinson KM, Alcorn JF
Title A tale of two cytokines: IL-17 and IL-22 in asthma and infection.
Journal Reference Authors Sha Y, Markovic-Plese S
Title A role of IL-1R1 signaling in the differentiation of Th17 cells and the development of autoimmune diseases.
Journal Reference Authors Nakayama T, Yamashita M
Title The TCR-mediated signaling pathways that control the direction of helper T cell differentiation.
Journal Reference Authors Lazarevic V, Chen X, Shim JH, Hwang ES, Jang E, Bolm AN, Oukka M, Kuchroo VK, Glimcher LH
Title T-bet represses T(H)17 differentiation by preventing Runx1-mediated activation of the gene encoding RORgammat.
Journal Reference Authors Pan F, Barbi J, Pardoll DM
Title Hypoxia-inducible factor 1: A link between metabolism and T cell differentiation and a potential therapeutic target.
Journal Reference Authors Veldhoen M, Hirota K, Westendorf AM, Buer J, Dumoutier L, Renauld JC, Stockinger B
Title The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins.
Journal Reference Authors Deenick EK, Tangye SG
Title Autoimmunity: IL-21: a new player in Th17-cell differentiation.
Journal Reference Authors Meka RR, Venkatesha SH, Dudics S, Acharya B, Moudgil KD
Title IL-27-induced modulation of autoimmunity and its therapeutic potential.
Journal Reference Authors Park H, Li Z, Yang XO, Chang SH, Nurieva R, Wang YH, Wang Y, Hood L, Zhu Z, Tian Q, Dong C
Title A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17.
Journal Reference Authors Zhu S, Qian Y
Title IL-17/IL-17 receptor system in autoimmune disease: mechanisms and therapeutic potential.
Journal Related myb04620 Toll-like receptor signaling pathway
myb04660 T cell receptor signaling pathway
KO pathway LinkDB All DBs
