KEGG   PATHWAY: uah04658
Entry
uah04658                    Pathway                                

Name
Th1 and Th2 cell differentiation - Ursus arctos horribilis
Description
Immunity to different classes of microorganisms is orchestrated by separate lineages of effector T helper (TH)-cells, which differentiate from naive CD4+ precursor cells in response to cues provided by antigen presenting cells (APC) and include T helper type 1 (Th1) and Th2. Th1 cells are characterized by the transcription factor T-bet and signal transducer and activator of transcription (STAT) 4, and the production of IFN-gamma. These cells stimulate strong cell-mediated immune responses, particularly against intracellular pathogens. On the other hand, transcription factors like GATA-3 and STAT6 drive the generation of Th2 cells that produce IL-4, IL-5 and IL-13 and are necessary for inducing the humoral response to combat parasitic helminths (type 2 immunity) and isotype switching to IgG1 and IgE. The balance between Th1/Th2 subsets determines the susceptibility to disease states, where the improper development of Th2 cells can lead to allergy, while an overactive Th1 response can lead to autoimmunity.
Class
Organismal Systems; Immune system
Pathway map
uah04658  Th1 and Th2 cell differentiation
uah04658

Other DBs
GO: 0045063 0045064
Organism
Ursus arctos horribilis [GN:uah]
Gene
113243222  DLL3; delta-like protein 3 [KO:K06051]
113242017  DLL4; delta-like protein 4 [KO:K06051]
113247092  DLL1; delta-like protein 1 isoform X1 [KO:K06051]
113248714  NOTCH3; neurogenic locus notch homolog protein 3 isoform X1 [KO:K20995]
113255691  MAML3; mastermind-like protein 3 [KO:K06061]
113259807  MAML2; mastermind-like protein 2 isoform X1 [KO:K06061]
113261557  MAML1; mastermind-like protein 1 [KO:K06061]
113258648  RBPJL; recombining binding protein suppressor of hairless-like protein [KO:K06053]
113266766  RBPJ; recombining binding protein suppressor of hairless isoform X1 [KO:K06053]
113263101  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
113244102  RELA; transcription factor p65 [KO:K04735]
113256304  IFNG; interferon gamma [KO:K04687]
113259485  IFNGR1; interferon gamma receptor 1 [KO:K05132]
113264675  IFNGR2; interferon gamma receptor 2 [KO:K05133]
113254577  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
113270160  JAK2; tyrosine-protein kinase JAK2 isoform X1 [KO:K04447] [EC:2.7.10.2]
113250654  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
113254130  IL12A; interleukin-12 subunit alpha [KO:K05406]
113263879  IL12B; interleukin-12 subunit beta [KO:K05425]
113256701  IL12RB1; interleukin-12 receptor subunit beta-1 isoform X1 [KO:K05063]
113254551  IL12RB2; interleukin-12 receptor subunit beta-2 [KO:K05064]
113242985  TYK2; non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
113250651  STAT4; signal transducer and activator of transcription 4 [KO:K11222]
113265555  TBX21; T-box transcription factor TBX21 [KO:K10166]
113268494  RUNX3; runt-related transcription factor 3 isoform X1 [KO:K09279]
113243684  LOW QUALITY PROTEIN: HLA class II histocompatibility antigen, DP alpha 1 chain-like [KO:K06752]
113243685  LOW QUALITY PROTEIN: HLA class II histocompatibility antigen, DP beta 1 chain-like [KO:K06752]
113243774  HLA class II histocompatibility antigen, DR alpha chain [KO:K06752]
113243775  DLA class II histocompatibility antigen, DR-1 beta chain [KO:K06752]
113243776  SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like [KO:K06752]
113243777  HLA class II histocompatibility antigen, DQ beta 1 chain-like [KO:K06752]
113243778  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
113243779  HLA class II histocompatibility antigen, DO beta chain isoform X1 [KO:K06752]
113243784  HLA class II histocompatibility antigen, DM beta chain isoform X1 [KO:K06752]
113243786  HLA class II histocompatibility antigen, DM alpha chain isoform X1 [KO:K06752]
113243788  HLA class II histocompatibility antigen, DO alpha chain [KO:K06752]
113257962  CD4; T-cell surface glycoprotein CD4 isoform X1 [KO:K06454]
113268359  LCK; tyrosine-protein kinase Lck [KO:K05856] [EC:2.7.10.2]
113260003  CD3E; T-cell surface glycoprotein CD3 epsilon chain [KO:K06451]
113260001  CD3G; T-cell surface glycoprotein CD3 gamma chain [KO:K06452]
113265359  uncharacterized protein LOC113265359 [KO:K10785]
113262884  CD247; T-cell surface glycoprotein CD3 zeta chain isoform X1 [KO:K06453]
113260002  CD3D; T-cell surface glycoprotein CD3 delta chain [KO:K06450]
113246717  tyrosine-protein kinase ZAP-70 [KO:K07360] [EC:2.7.10.2]
113267622  LAT; LOW QUALITY PROTEIN: linker for activation of T-cells family member 1 [KO:K07362]
113258609  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
113270001  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
113259177  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
113263105  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
113244743  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
113260378  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
113253544  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
113258729  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
113252399  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
113241147  PRKCQ; protein kinase C theta type isoform X1 [KO:K18052] [EC:2.7.11.13]
113251823  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
113245546  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
113247832  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
113266131  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
113243600  NFKBIB; NF-kappa-B inhibitor beta isoform X1 [KO:K02581]
113261039  NFKBIE; NF-kappa-B inhibitor epsilon [KO:K05872]
113267646  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
113247020  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
113270317  FOS; proto-oncogene c-Fos [KO:K04379]
113241613  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
113241615  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
113243852  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
113243854  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
113263180  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
113261548  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
113243106  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
113254611  JUN; transcription factor AP-1 [KO:K04448]
113255635  IL2; interleukin-2 [KO:K05429]
113241140  IL2RA; interleukin-2 receptor subunit alpha isoform X1 [KO:K05068]
113249383  interleukin-2 receptor subunit beta-like isoform X1 [KO:K05069]
113249385  interleukin-2 receptor subunit beta-like isoform X1 [KO:K05069]
113245610  IL2RG; cytokine receptor common subunit gamma isoform X1 [KO:K05070]
113256691  JAK3; tyrosine-protein kinase JAK3 [KO:K11218] [EC:2.7.10.2]
113265423  STAT5A; signal transducer and activator of transcription 5A isoform X1 [KO:K11223]
113265424  signal transducer and activator of transcription 5B isoform X1 [KO:K11224]
113261716  IL4; interleukin-4 [KO:K05430]
113267608  IL4R; interleukin-4 receptor subunit alpha isoform X1 [KO:K05071]
113256394  STAT6; signal transducer and activator of transcription 6 isoform X1 [KO:K11225]
113241157  GATA3; trans-acting T-cell-specific transcription factor GATA-3 isoform X1 [KO:K17895]
113261714  IL5; interleukin-5 [KO:K05428]
113261717  IL13; interleukin-13 [KO:K05435]
113251743  MAF; transcription factor Maf [KO:K09035]
113258337  JAG1; protein jagged-1 isoform X1 [KO:K06052]
113267148  JAG2; protein jagged-2 [KO:K21635]
113248585  neurogenic locus notch homolog protein 1 [KO:K02599]
113248639  neurogenic locus notch homolog protein 1-like [KO:K02599]
113244432  NOTCH2; neurogenic locus notch homolog protein 2 [KO:K20994]
Compound
C00076  Calcium cation
C00165  Diacylglycerol
C01245  D-myo-Inositol 1,4,5-trisphosphate
Reference
  Authors
Amsen D, Spilianakis CG, Flavell RA
  Title
How are T(H)1 and T(H)2 effector cells made?
  Journal
Curr Opin Immunol 21:153-60 (2009)
DOI:10.1016/j.coi.2009.03.010
Reference
  Authors
Knosp CA, Johnston JA
  Title
Regulation of CD4+ T-cell polarization by suppressor of cytokine signalling proteins.
  Journal
Immunology 135:101-11 (2012)
DOI:10.1111/j.1365-2567.2011.03520.x
Reference
  Authors
Dong C, Flavell RA
  Title
Control of T helper cell differentiation--in search of master genes.
  Journal
Sci STKE 2000:pe1 (2000)
DOI:10.1126/stke.2000.49.pe1
Reference
  Authors
O'Garra A, Arai N
  Title
The molecular basis of T helper 1 and T helper 2 cell differentiation.
  Journal
Trends Cell Biol 10:542-50 (2000)
DOI:10.1016/S0962-8924(00)01856-0
Reference
  Authors
Hong CC, Yao S, McCann SE, Dolnick RY, Wallace PK, Gong Z, Quan L, Lee KP, Evans SS, Repasky EA, Edge SB, Ambrosone CB
  Title
Pretreatment levels of circulating Th1 and Th2 cytokines, and their ratios, are associated with ER-negative and triple negative breast cancers.
  Journal
Breast Cancer Res Treat 139:477-88 (2013)
DOI:10.1007/s10549-013-2549-3
Reference
  Authors
Kolls JK
  Title
CD4(+) T-cell subsets and host defense in the lung.
  Journal
Immunol Rev 252:156-63 (2013)
DOI:10.1111/imr.12030
Reference
  Authors
Zhu J, Paul WE
  Title
Peripheral CD4+ T-cell differentiation regulated by networks of cytokines and transcription factors.
  Journal
Immunol Rev 238:247-62 (2010)
DOI:10.1111/j.1600-065X.2010.00951.x
Reference
  Authors
Wilson CB, Rowell E, Sekimata M
  Title
Epigenetic control of T-helper-cell differentiation.
  Journal
Nat Rev Immunol 9:91-105 (2009)
DOI:10.1038/nri2487
Reference
  Authors
Callard RE, Yates AJ
  Title
Immunology and mathematics: crossing the divide.
  Journal
Immunology 115:21-33 (2005)
DOI:10.1111/j.1365-2567.2005.02142.x
Reference
  Authors
Lazarevic V, Glimcher LH, Lord GM
  Title
T-bet: a bridge between innate and adaptive immunity.
  Journal
Nat Rev Immunol 13:777-89 (2013)
DOI:10.1038/nri3536
Reference
  Authors
Weigmann B, Neurath MF
  Title
T-bet and mucosal Th1 responses in the gastrointestinal tract.
  Journal
Gut 51:301-3 (2002)
DOI:10.1136/gut.51.3.301
Reference
  Authors
Adamson AS, Collins K, Laurence A, O'Shea JJ
  Title
The Current STATus of lymphocyte signaling: new roles for old players.
  Journal
Curr Opin Immunol 21:161-6 (2009)
DOI:10.1016/j.coi.2009.03.013
Reference
  Authors
Zhu J
  Title
Transcriptional regulation of Th2 cell differentiation.
  Journal
Immunol Cell Biol 88:244-9 (2010)
DOI:10.1038/icb.2009.114
Reference
  Authors
Zhu J
  Title
T helper 2 (Th2) cell differentiation, type 2 innate lymphoid cell (ILC2) development and regulation of interleukin-4 (IL-4) and IL-13 production.
  Journal
Cytokine 75:14-24 (2015)
DOI:10.1016/j.cyto.2015.05.010
Reference
  Authors
Ho IC, Tai TS, Pai SY
  Title
GATA3 and the T-cell lineage: essential functions before and after T-helper-2-cell differentiation.
  Journal
Nat Rev Immunol 9:125-35 (2009)
DOI:10.1038/nri2476
Reference
  Authors
Amsen D, Antov A, Flavell RA
  Title
The different faces of Notch in T-helper-cell differentiation.
  Journal
Nat Rev Immunol 9:116-24 (2009)
DOI:10.1038/nri2488
Reference
  Authors
Pahan K, Mondal S
  Title
Crosstalk between Nitric Oxide and T helper cells.
  Journal
J Clin Cell Immunol 3:e109 (2012)
Reference
  Authors
Schmidt A, Oberle N, Krammer PH
  Title
Molecular mechanisms of treg-mediated T cell suppression.
  Journal
Front Immunol 3:51 (2012)
DOI:10.3389/fimmu.2012.00051
Related
pathway
uah04010  MAPK signaling pathway
uah04020  Calcium signaling pathway
uah04064  NF-kappa B signaling pathway
uah04330  Notch signaling pathway
uah04514  Cell adhesion molecules (CAMs)
uah04630  JAK-STAT signaling pathway
uah04660  T cell receptor signaling pathway
KO pathway
ko04658   
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