Entry Name Th17 cell differentiation - Loxodonta africana (African savanna elephant)
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 Loxodonta africana (African savanna elephant) [GN:
lav ]
Gene 100666654 IL1RAP; interleukin-1 receptor accessory protein isoform X2 [KO:K04723 ]
100663495 SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500 ]
100664834 IL2RG; cytokine receptor common subunit gamma isoform X1 [KO:K05070 ]
100669556 IL6ST; interleukin-6 receptor subunit beta isoform X2 [KO:K05060 ]
100672726 IL12RB1; interleukin-12 receptor subunit beta-1 isoform X1 [KO:K05063 ]
100669583 STAT3; signal transducer and activator of transcription 3 isoform X2 [KO:K04692 ]
100676217 HSP90AA1; LOW QUALITY PROTEIN: heat shock protein HSP 90-alpha [KO:K04079 ]
100672091 HLA class II histocompatibility antigen, DO alpha chain isoform X1 [KO:K06752 ]
100672379 HLA class II histocompatibility antigen, DM alpha chain [KO:K06752 ]
100664409 HLA class II histocompatibility antigen, DQ alpha 2 chain-like [KO:K06752 ]
100665293 HLA class II histocompatibility antigen, DRB1-4 beta chain-like [KO:K06752 ]
100662176 HLA class II histocompatibility antigen, DP alpha 1 chain-like isoform X4 [KO:K06752 ]
100668794 HLA class II histocompatibility antigen, DQ beta 2 chain-like isoform X2 [KO:K06752 ]
100673529 HLA class II histocompatibility antigen, DO beta chain [KO:K06752 ]
100675728 DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752 ]
100669075 LOW QUALITY PROTEIN: HLA class II histocompatibility antigen, DQ beta 1 chain-like [KO:K06752 ]
100666146 HLA class II histocompatibility antigen, DR alpha chain-like [KO:K06752 ]
100665860 DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752 ]
100675445 LOW QUALITY PROTEIN: HLA class II histocompatibility antigen, DR alpha chain-like [KO:K06752 ]
100667002 LOW QUALITY PROTEIN: HLA class II histocompatibility antigen, DR alpha chain-like [KO:K06752 ]
100664981 LOW QUALITY PROTEIN: HLA class II histocompatibility antigen, DR alpha chain-like [KO:K06752 ]
100665266 LOW QUALITY PROTEIN: mamu class II histocompatibility antigen, DR alpha chain-like [KO:K06752 ]
100671834 HLA class II histocompatibility antigen, DP beta 1 chain-like [KO:K06752 ]
111748122 SLA class II histocompatibility antigen, DQ haplotype C beta chain-like [KO:K06752 ]
100672669 HLA class II histocompatibility antigen, DM beta chain isoform X1 [KO:K06752 ]
100674958 mamu class II histocompatibility antigen, DR alpha chain [KO:K06752 ]
100665550 LOW QUALITY PROTEIN: HLA class II histocompatibility antigen, DR alpha chain-like [KO:K06752 ]
100665834 DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752 ]
111748125 HLA class II histocompatibility antigen, DP beta 1 chain-like [KO:K06752 ]
100671798 LOW QUALITY PROTEIN: HLA class II histocompatibility antigen, DP alpha 1 chain [KO:K06752 ]
100673824 HLA class II histocompatibility antigen, DQ beta 2 chain-like [KO:K06752 ]
100659676 DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752 ]
100675007 CD4; LOW QUALITY PROTEIN: T-cell surface glycoprotein CD4 [KO:K06454 ]
100654724 CD3E; T-cell surface glycoprotein CD3 epsilon chain isoform X1 [KO:K06451 ]
100661940 CD3G; T-cell surface glycoprotein CD3 gamma chain isoform X1 [KO:K06452 ]
100675602 LAT; linker for activation of T-cells family member 1 [KO:K07362 ]
100677739 PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116 ] [EC:3.1.4.11 ]
100661626 PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform [KO:K04348 ] [EC:3.1.3.16 ]
100664832 PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
100677352 PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
100655623 NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X3 [KO:K04446 ]
100672662 NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332 ]
100658037 NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X2 [KO:K17333 ]
100661492 IKBKG; LOW QUALITY PROTEIN: NF-kappa-B essential modulator [KO:K07210 ]
100662194 NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580 ]
100675819 STAT6; signal transducer and activator of transcription 6 isoform X1 [KO:K11225 ]
100655161 GATA3; LOW QUALITY PROTEIN: trans-acting T-cell-specific transcription factor GATA-3 [KO:K17895 ]
100665882 RUNX1; runt-related transcription factor 1 isoform X1 [KO:K08367 ]
100668424 STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220 ]
100676521 TBX21; LOW QUALITY PROTEIN: T-box transcription factor TBX21 [KO:K10166 ]
100669139 IL2RB; interleukin-2 receptor subunit beta isoform X1 [KO:K05069 ]
100669299 STAT5B; signal transducer and activator of transcription 5B isoform X1 [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 lav04620 Toll-like receptor signaling pathway
lav04660 T cell receptor signaling pathway
KO pathway LinkDB All DBs
