Th2 Pathway
The initial step of differentiation of the naive T-cells is the antigenic stimulation as a result of interaction of the genetically variable TCR and co-receptor CD4 with antigen-MHC II complex, presented by professional antigen presenting cells (APCs). Upon activation by T cell receptor (TCR)- and cytokine-mediated signaling, naive CD4+ T cells may differentiate into at least five major types of T helper (Th) cells, Th1, Th2, Th17, Tfh, and inducible T regulatory (iTreg) cells, that play a critical role in orchestrating adaptive immune responses to various microorganisms. A lack of sufficient stimulation from secondary signals like the cytokines, CD28, and Notch at this point may conversely lead to anergy or even apoptosis.To initiate Th2 differentiation, many cytokines including IL-4, IL-2, IL-7 and thymic stromal lymphopoietin (TSLP) may be involved, though eventually IL4 plays the leading role in autocrine self-reinforcement. T-cell receptor activation causes two parallel events in cells destined for the Th2 fate...
Pathway Summary
The initial step of differentiation of the naive T-cells is the antigenic stimulation as a result of interaction of the genetically variable TCR and co-receptor CD4 with antigen-MHC II complex, presented by professional antigen presenting cells (APCs). Upon activation by T cell receptor (TCR)- and cytokine-mediated signaling, naive CD4+ T cells may differentiate into at least five major types of T helper (Th) cells, Th1, Th2, Th17, Tfh, and inducible T regulatory (iTreg) cells, that play a critical role in orchestrating adaptive immune responses to various microorganisms. A lack of sufficient stimulation from secondary signals like the cytokines, CD28, and Notch at this point may conversely lead to anergy or even apoptosis.To initiate Th2 differentiation, many cytokines including IL-4, IL-2, IL-7 and thymic stromal lymphopoietin (TSLP) may be involved, though eventually IL4 plays the leading role in autocrine self-reinforcement. T-cell receptor activation causes two parallel events in cells destined for the Th2 fate. It directly stimulates a modest but significant increase in Gata3 mRNA, which rises steadily until ~24h after stimulation. In parallel, TCR engagement induces IL-2 production, which, in turn activates Stat5. The combination of early Stat5 activation and Gata3 induction leads to IL-4 production. This 'early IL-4' is TCR dependent but IL-4 independent. However, once the 'early IL-4' accumulates sufficiently, it signals through the IL-4R/Stat6 pathway to strikingly upregulate Gata3, which together with continued Stat5 activation, results in a further upregulation of IL-4 mRNA and thus to a positive feedback loop that results in the commitment to the Th2 phenotype.The essential transcription factors of Th lineages are T-bet/Stat4 (Th1), Gata3/Stat5 (Th2), RORγt/Stat3 (Th17), and Foxp3/Stat5 (iTreg), respectively. T-bet is regarded as the master regulator for Th1 cell differentiation and IFNγ production. Th2 helper cells are host immunity effectors against extracellular parasites including helminths. They are triggered by IL-4 and their effector cytokines are IL-4, IL-5, IL-9, IL-10 and IL-13. They partner with B-cells, eosinophils, and mast cells to make humoral antibodies and granulocytic responses to large pathogens.
Th2 Pathway Genes list
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ACVR1activin A receptor type 1 ACVR1Bactivin A receptor type 1B ACVR1Cactivin A receptor type 1C ACVR2Aactivin A receptor type 2A ACVR2Bactivin A receptor type 2B APH1Aaph-1 homolog A, gamma-secretase subunit APH1Baph-1 homolog B, gamma-secretase subunit B2Mbeta-2-microglobulin BHLHE41basic helix-loop-helix family member e41 BMPR2bone morphogenetic protein receptor type 2 CCR1C-C motif chemokine receptor 1 CCR3C-C motif chemokine receptor 3 CCR4C-C motif chemokine receptor 4 CCR5C-C motif chemokine receptor 5 CCR8C-C motif chemokine receptor 8 CD247CD247 molecule CD28CD28 molecule CD3DCD3d molecule CD3ECD3e molecule CD3GCD3g molecule CD4CD4 molecule CD40CD40 molecule CD80CD80 molecule CD86CD86 molecule CHD4chromodomain helicase DNA binding protein 4 CRLF2cytokine receptor like factor 2 CXCR4C-X-C motif chemokine receptor 4 CXCR6C-X-C motif chemokine receptor 6 DLL1delta like canonical Notch ligand 1 GATA3GATA binding protein 3 GFI1growth factor independent 1 transcriptional repressor GRB2growth factor receptor bound protein 2 HAVCR1hepatitis A virus cellular receptor 1 HLA-Amajor histocompatibility complex, class I, A HLA-Bmajor histocompatibility complex, class I, B HLA-Cmajor histocompatibility complex, class I, C HLA-DMAmajor histocompatibility complex, class II, DM alpha HLA-DMBmajor histocompatibility complex, class II, DM beta HLA-DOAmajor histocompatibility complex, class II, DO alpha HLA-DOBmajor histocompatibility complex, class II, DO beta HLA-DPA1major histocompatibility complex, class II, DP alpha 1 HLA-DPB1major histocompatibility complex, class II, DP beta 1 HLA-DQA1major histocompatibility complex, class II, DQ alpha 1 HLA-DQA2major histocompatibility complex, class II, DQ alpha 2 HLA-DQB1major histocompatibility complex, class II, DQ beta 1 HLA-DQB2major histocompatibility complex, class II, DQ beta 2 HLA-DQB3major histocompatibility complex, class II, DQ beta 3 HLA-DRAmajor histocompatibility complex, class II, DR alpha HLA-DRB1major histocompatibility complex, class II, DR beta 1 HLA-DRB3major histocompatibility complex, class II, DR beta 3 HLA-DRB4major histocompatibility complex, class II, DR beta 4 HLA-DRB5major histocompatibility complex, class II, DR beta 5 HLA-Emajor histocompatibility complex, class I, E HLA-Fmajor histocompatibility complex, class I, F HLA-Gmajor histocompatibility complex, class I, G ICAM1intercellular adhesion molecule 1 ICOSinducible T cell costimulator ICOSLGinducible T cell costimulator ligand IFNGinterferon gamma IKZF1IKAROS family zinc finger 1 IL10interleukin 10 IL12Ainterleukin 12A IL12Binterleukin 12B IL12RB1interleukin 12 receptor subunit beta 1 IL12RB2interleukin 12 receptor subunit beta 2 IL13interleukin 13 IL17RBinterleukin 17 receptor B IL1RL1interleukin 1 receptor like 1 IL2interleukin 2 IL24interleukin 24 IL25interleukin 25 IL2RAinterleukin 2 receptor subunit alpha IL2RBinterleukin 2 receptor subunit beta IL2RGinterleukin 2 receptor subunit gamma IL3interleukin 3 IL31interleukin 31 IL33interleukin 33 IL4interleukin 4 IL4Rinterleukin 4 receptor IL5interleukin 5 IL9interleukin 9 ITGB2integrin subunit beta 2 JAG1jagged canonical Notch ligand 1 JAG2jagged canonical Notch ligand 2 JAK1Janus kinase 1 JAK2Janus kinase 2 JAK3Janus kinase 3 JUNJun proto-oncogene, AP-1 transcription factor subunit MAFMAF bZIP transcription factor MIR155microRNA 155 MIR21microRNA 21 NCSTNnicastrin NFATC2nuclear factor of activated T cells 2 NFKB1nuclear factor kappa B subunit 1 NOTCH1notch receptor 1 NOTCH2notch receptor 2 NOTCH3notch receptor 3 NOTCH4notch receptor 4 PIK3C2Aphosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 alpha PIK3C2Bphosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 beta PIK3C2Gphosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 gamma PIK3C3phosphatidylinositol 3-kinase catalytic subunit type 3 PIK3CAphosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha PIK3CBphosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta PIK3CDphosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta PIK3CGphosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma PIK3R1phosphoinositide-3-kinase regulatory subunit 1 PIK3R2phosphoinositide-3-kinase regulatory subunit 2 PIK3R3phosphoinositide-3-kinase regulatory subunit 3 PIK3R4phosphoinositide-3-kinase regulatory subunit 4 PIK3R5phosphoinositide-3-kinase regulatory subunit 5 PIK3R6phosphoinositide-3-kinase regulatory subunit 6 PRKCQprotein kinase C theta PSEN1presenilin 1 PSEN2presenilin 2 PSENENpresenilin enhancer, gamma-secretase subunit PTGDR2prostaglandin D2 receptor 2 RUNX3RUNX family transcription factor 3 S1PR1sphingosine-1-phosphate receptor 1 SOCS3suppressor of cytokine signaling 3 SPI1Spi-1 proto-oncogene STAT4signal transducer and activator of transcription 4 STAT5Asignal transducer and activator of transcription 5A STAT5Bsignal transducer and activator of transcription 5B STAT6signal transducer and activator of transcription 6 TBX21T-box transcription factor 21 TGFB1transforming growth factor beta 1 TGFBR1transforming growth factor beta receptor 1 TGFBR2transforming growth factor beta receptor 2 TGFBR3transforming growth factor beta receptor 3 TIMD4T cell immunoglobulin and mucin domain containing 4 TNFRSF4TNF receptor superfamily member 4 TNFSF4TNF superfamily member 4 TSLPthymic stromal lymphopoietin TYK2tyrosine kinase 2 VAV1vav guanine nucleotide exchange factor 1
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