Entry Name Th17 cell differentiation - Equus caballus (horse)
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 Equus caballus (horse) [GN:
ecb ]
Gene 100068726 IL1RAP; interleukin-1 receptor accessory protein isoform X3 [KO:K04723 ]
100033843 SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500 ]
100033845 SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605 ]
102148787 IL6R; interleukin-6 receptor subunit alpha isoform X2 [KO:K05055 ]
100146965 IL12RB1; interleukin-12 receptor subunit beta-1 isoform X1 [KO:K05063 ]
100034011 STAT3; signal transducer and activator of transcription 3 [KO:K04692 ]
100061035 HLA class II histocompatibility antigen, DM alpha chain-like precursor [KO:K06752 ]
100060770 HLA class II histocompatibility antigen, DO beta chain isoform X1 [KO:K06752 ]
100061127 HLA class II histocompatibility antigen, DO alpha chain [KO:K06752 ]
100060996 HLA class II histocompatibility antigen, DM beta chain isoform X1 [KO:K06752 ]
100060531 HLA class II histocompatibility antigen, DQ beta 2 chain isoform X1 [KO:K06752 ]
111767457 DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752 ]
100060697 DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752 ]
100051432 CD247; T-cell surface glycoprotein CD3 zeta chain isoform X1 [KO:K06453 ]
100064430 LAT; linker for activation of T-cells family member 1 [KO:K07362 ]
100070545 PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X3 [KO:K01116 ] [EC:3.1.4.11 ]
100057357 PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
100067434 PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X4 [KO:K04348 ] [EC:3.1.3.16 ]
100072862 PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
100065378 NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446 ]
100052657 NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X4 [KO:K17332 ]
100053856 NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333 ]
100067767 NFKBIE; LOW QUALITY PROTEIN: NF-kappa-B inhibitor epsilon [KO:K05872 ]
100067894 NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X4 [KO:K02580 ]
791252 IL4R; interleukin-4 receptor subunit alpha precursor [KO:K05071 ]
100050053 STAT6; signal transducer and activator of transcription 6 [KO:K11225 ]
100069946 GATA3; trans-acting T-cell-specific transcription factor GATA-3 isoform X2 [KO:K17895 ]
100051950 RUNX1; runt-related transcription factor 1 isoform X1 [KO:K08367 ]
100069633 STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220 ]
100070292 IL2RA; interleukin-2 receptor subunit alpha precursor [KO:K05068 ]
100069676 IL2RB; interleukin-2 receptor subunit beta isoform X2 [KO:K05069 ]
100052904 STAT5A; signal transducer and activator of transcription 5A isoform X1 [KO:K11223 ]
100052954 signal transducer and activator of transcription 5B isoform X3 [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 ecb04620 Toll-like receptor signaling pathway
ecb04660 T cell receptor signaling pathway
KO pathway LinkDB All DBs
