Entry Name Th17 cell differentiation - Trichechus manatus latirostris (Florida manatee)
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 Trichechus manatus latirostris (Florida manatee) [GN:
tmu ]
Gene 101342651 signal transducer and activator of transcription 3 isoform X3 [KO:K04692 ]
101348117 LOW QUALITY PROTEIN: heat shock protein HSP 90-alpha-like [KO:K04079 ]
101343312 HLA class II histocompatibility antigen, DM alpha chain isoform X1 [KO:K06752 ]
101343065 HLA class II histocompatibility antigen, DO alpha chain [KO:K06752 ]
101344101 LOW QUALITY PROTEIN: boLa class II histocompatibility antigen, DQB*0101 beta chain-like [KO:K06752 ]
101345015 boLa class II histocompatibility antigen, DQB*0101 beta chain-like [KO:K06752 ]
101361245 LOW QUALITY PROTEIN: DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752 ]
101342567 HLA class II histocompatibility antigen, DP beta 1 chain [KO:K06752 ]
101342817 HLA class II histocompatibility antigen, DP alpha 1 chain isoform X2 [KO:K06752 ]
101342571 HLA class II histocompatibility antigen, DP beta 1 chain-like [KO:K06752 ]
101343573 HLA class II histocompatibility antigen, DM beta chain [KO:K06752 ]
101345267 HLA class II histocompatibility antigen, DQ alpha 2 chain-like [KO:K06752 ]
101345522 HLA class II histocompatibility antigen, DR alpha chain [KO:K06752 ]
101348755 HLA class II histocompatibility antigen, DP alpha 1 chain-like [KO:K06752 ]
101359660 T-cell surface glycoprotein CD3 epsilon chain isoform X1 [KO:K06451 ]
101352744 T-cell surface glycoprotein CD3 gamma chain isoform X1 [KO:K06452 ]
101361451 LOW QUALITY PROTEIN: uncharacterized protein LOC101361451 [KO:K10785 ]
101345999 T-cell surface glycoprotein CD3 zeta chain isoform X1 [KO:K06453 ]
101353008 T-cell surface glycoprotein CD3 delta chain isoform X1 [KO:K06450 ]
101356413 linker for activation of T-cells family member 1 isoform X2 [KO:K07362 ]
101353424 serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X2 [KO:K04348 ] [EC:3.1.3.16 ]
101357894 serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
101359059 nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446 ]
101355751 nuclear factor of activated T-cells, cytoplasmic 2 isoform X2 [KO:K17332 ]
101352434 nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333 ]
101354015 trans-acting T-cell-specific transcription factor GATA-3 isoform X2 [KO:K17895 ]
101357916 signal transducer and activator of transcription 1-alpha/beta [KO:K11220 ]
101343407 signal transducer and activator of transcription 5A isoform X1 [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 tmu04620 Toll-like receptor signaling pathway
tmu04660 T cell receptor signaling pathway
KO pathway LinkDB All DBs
