Entry Name Th17 cell differentiation - Artibeus jamaicensis (Jamaican fruit-eating 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 Artibeus jamaicensis (Jamaican fruit-eating bat) [GN:
ajm ]
Gene 119057106 SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605 ]
119035395 IL2RG; cytokine receptor common subunit gamma isoform X1 [KO:K05070 ]
119049182 IL6ST; interleukin-6 receptor subunit beta isoform X1 [KO:K05060 ]
119052142 STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692 ]
119041136 LOW QUALITY PROTEIN: putative heat shock protein HSP 90-beta-3 [KO:K04079 ]
119038537 HLA class II histocompatibility antigen, DQ beta 2 chain-like [KO:K06752 ]
119040562 SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like [KO:K06752 ]
119040793 SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like [KO:K06752 ]
119040794 SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like [KO:K06752 ]
119052984 HLA class II histocompatibility antigen, DM beta chain [KO:K06752 ]
119052987 HLA class II histocompatibility antigen, DM alpha chain isoform X1 [KO:K06752 ]
119060698 LOW QUALITY PROTEIN: HLA class II histocompatibility antigen, DP alpha 1 chain-like [KO:K06752 ]
119061214 H-2 class II histocompatibility antigen, A-D beta chain-like [KO:K06752 ]
119062087 DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752 ]
119055692 DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752 ]
119055693 H-2 class II histocompatibility antigen, E-S beta chain-like [KO:K06752 ]
119055694 HLA class II histocompatibility antigen, DR alpha chain-like [KO:K06752 ]
119048626 rano class II histocompatibility antigen, A beta chain-like [KO:K06752 ]
119056744 DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752 ]
119056745 HLA class II histocompatibility antigen, DR alpha chain-like [KO:K06752 ]
119049925 HLA class II histocompatibility antigen, DR alpha chain-like [KO:K06752 ]
119057940 SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like [KO:K06752 ]
119050803 CD3G; T-cell surface glycoprotein CD3 gamma chain isoform X1 [KO:K06452 ]
119065449 CD247; T-cell surface glycoprotein CD3 zeta chain isoform X1 [KO:K06453 ]
119050808 CD3D; T-cell surface glycoprotein CD3 delta chain isoform X1 [KO:K06450 ]
119045357 LAT; linker for activation of T-cells family member 1 isoform X1 [KO:K07362 ]
119063199 PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116 ] [EC:3.1.4.11 ]
119038093 PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
119054082 PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
119054654 PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
119051373 NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446 ]
119040619 NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332 ]
119061858 NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333 ]
119057921 NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580 ]
119035652 STAT6; signal transducer and activator of transcription 6 isoform X1 [KO:K11225 ]
119052973 GATA3; trans-acting T-cell-specific transcription factor GATA-3 isoform X1 [KO:K17895 ]
119035732 RUNX1; runt-related transcription factor 1 isoform X1 [KO:K08367 ]
119049688 IL27RA; interleukin-27 receptor subunit alpha isoform X1 [KO:K19598 ]
119062093 STAT1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220 ]
119048017 IL2RA; interleukin-2 receptor subunit alpha isoform X1 [KO:K05068 ]
119052172 STAT5A; signal transducer and activator of transcription 5A [KO:K11223 ]
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 ajm04620 Toll-like receptor signaling pathway
ajm04660 T cell receptor signaling pathway
KO pathway LinkDB All DBs
