Entry Name Th17 cell differentiation - Canis lupus familiaris (dog)
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 Canis lupus familiaris (dog) [GN:
cfa ]
Gene 481328 IL1R1; interleukin-1 receptor type 1 isoform X1 [KO:K04386 ]
488126 IL1RAP; interleukin-1 receptor accessory protein isoform X2 [KO:K04723 ]
403998 TGFB1; transforming growth factor beta-1 proprotein isoform X1 [KO:K13375 ]
480144 SMAD2; mothers against decapentaplegic homolog 2 isoform X1 [KO:K04500 ]
610902 SMAD3; mothers against decapentaplegic homolog 3 [KO:K23605 ]
476196 SMAD4; mothers against decapentaplegic homolog 4 isoform X2 [KO:K04501 ]
403851 IL2RG; cytokine receptor common subunit gamma precursor [KO:K05070 ]
612271 IL6R; interleukin-6 receptor subunit alpha isoform X3 [KO:K05055 ]
403545 IL6ST; interleukin-6 receptor subunit beta precursor [KO:K05060 ]
484828 IL12RB1; interleukin-12 receptor subunit beta-1 isoform X1 [KO:K05063 ]
490967 STAT3; signal transducer and activator of transcription 3 isoform X1 [KO:K04692 ]
483205 RORC; nuclear receptor ROR-gamma isoform X1 [KO:K08534 ]
480438 HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079 ]
100687242 LOW QUALITY PROTEIN: heat shock protein HSP 90-beta-like [KO:K04079 ]
474860 HLA-DRB1; DLA class II histocompatibility antigen, DR-1 beta chain precursor [KO:K06752 ]
481731 DLA-DRA; MHC class II DR alpha chain precursor [KO:K06752 ]
607786 DLA-DOB; major histocompatibility complex, class II, DO beta precursor [KO:K06752 ]
607827 DLA-DMB; major histocompatibility complex, class II, DM beta precursor [KO:K06752 ]
481732 DLA-DMA; major histocompatibility complex, class II, DM alpha precursor [KO:K06752 ]
474869 DLA-DOA; HLA class II histocompatibility antigen, DO alpha chain-like precursor [KO:K06752 ]
100856137 HLA class II histocompatibility antigen, DQ beta 2 chain isoform X1 [KO:K06752 ]
403931 CD4; T-cell surface glycoprotein CD4 precursor [KO:K06454 ]
442981 CD3E; T-cell surface glycoprotein CD3 epsilon chain isoform X1 [KO:K06451 ]
489383 CD3G; T-cell surface glycoprotein CD3 gamma chain [KO:K06452 ]
611571 CD247; T-cell surface glycoprotein CD3 zeta chain isoform X1 [KO:K06453 ]
479419 CD3D; T-cell surface glycoprotein CD3 delta chain [KO:K06450 ]
607947 LAT; linker for activation of T-cells family member 1 isoform X1 [KO:K07362 ]
485874 PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116 ] [EC:3.1.4.11 ]
609027 PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X3 [KO:K04348 ] [EC:3.1.3.16 ]
403486 PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform [KO:K04348 ] [EC:3.1.3.16 ]
479248 PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
612559 PPP3R1; calcineurin subunit B type 1 isoform X2 [KO:K06268 ]
610453 PPP3R2; calcineurin subunit B type 2 isoform X5 [KO:K06268 ]
483925 NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X3 [KO:K04446 ]
485930 NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332 ]
479678 NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333 ]
477796 CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X3 [KO:K04467 ] [EC:2.7.11.10 ]
482839 IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209 ] [EC:2.7.11.10 ]
484519 NFKBIB; NF-kappa-B inhibitor beta isoform X2 [KO:K02581 ]
442859 NFKB1; nuclear factor NF-kappa-B p105 subunit [KO:K02580 ]
483729 RELA; transcription factor p65 isoform X2 [KO:K04735 ]
489957 IL4R; interleukin-4 receptor subunit alpha isoform X2 [KO:K05071 ]
100142679 STAT6; signal transducer and activator of transcription 6 [KO:K11225 ]
487134 GATA3; trans-acting T-cell-specific transcription factor GATA-3 isoform X8 [KO:K17895 ]
487746 RUNX1; runt-related transcription factor 1 isoform X1 [KO:K08367 ]
607880 IL27; interleukin-27 subunit alpha isoform X1 [KO:K22629 ]
485043 EBI3; interleukin-27 subunit beta isoform X1 [KO:K24476 ]
484907 IL27RA; interleukin-27 receptor subunit alpha [KO:K19598 ]
487739 IFNGR2; interferon gamma receptor 2 isoform X3 [KO:K05133 ]
488449 STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220 ]
403870 IL2RA; interleukin-2 receptor subunit alpha precursor [KO:K05068 ]
403439 IL2RB; interleukin-2 receptor subunit beta isoform 2 precursor [KO:K05069 ]
490968 STAT5A; signal transducer and activator of transcription 5A isoform X2 [KO:K11223 ]
490969 STAT5B; signal transducer and activator of transcription 5B isoform X2 [KO:K11224 ]
491278 RXRA; retinoic acid receptor RXR-alpha isoform X1 [KO:K08524 ]
481735 RXRB; retinoic acid receptor RXR-beta isoform X1 [KO:K08525 ]
478989 RXRG; retinoic acid receptor RXR-gamma isoform X1 [KO:K08526 ]
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 cfa04620 Toll-like receptor signaling pathway
cfa04660 T cell receptor signaling pathway
KO pathway LinkDB All DBs
