KEGG   PATHWAY: pps04658
Entry
pps04658                    Pathway                                

Name
Th1 and Th2 cell differentiation - Pan paniscus (bonobo)
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
pps04658  Th1 and Th2 cell differentiation
pps04658

Other DBs
GO: 0045063 0045064
Organism
Pan paniscus (bonobo) [GN:pps]
Gene
100973086  DLL1; delta like canonical Notch ligand 1 [KO:K06051]
100981817  DLL4; delta like canonical Notch ligand 4 [KO:K06051]
100989211  DLL3; delta like canonical Notch ligand 3 [KO:K06051]
100984306  NOTCH3; notch 3 [KO:K20995]
100982217  MAML3; mastermind like transcriptional coactivator 3 [KO:K06061]
100984275  MAML1; mastermind like transcriptional coactivator 1 [KO:K06061]
100976416  MAML2; mastermind like transcriptional coactivator 2 [KO:K06061]
100969592  RBPJ; recombination signal binding protein for immunoglobulin kappa J region [KO:K06053]
100986827  RBPJL; recombination signal binding protein for immunoglobulin kappa J region like [KO:K06053]
100979341  NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]
100988429  RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735]
100991779  IFNG; interferon gamma [KO:K04687]
100994342  IFNGR1; interferon gamma receptor 1 [KO:K05132]
100988947  IFNGR2; interferon gamma receptor 2 [KO:K05133]
100972202  JAK1; Janus kinase 1 [KO:K11217] [EC:2.7.10.2]
100979742  JAK2; Janus kinase 2 [KO:K04447] [EC:2.7.10.2]
100971620  STAT1; signal transducer and activator of transcription 1 [KO:K11220]
100979574  IL12A; interleukin 12A [KO:K05406]
100989950  IL12B; interleukin 12B [KO:K05425]
100979712  IL12RB1; interleukin 12 receptor subunit beta 1 [KO:K05063]
100984257  IL12RB2; interleukin 12 receptor subunit beta 2 [KO:K05064]
100979090  TYK2; tyrosine kinase 2 [KO:K11219] [EC:2.7.10.2]
100972895  STAT4; signal transducer and activator of transcription 4 [KO:K11222]
100976185  TBX21; T-box 21 [KO:K10166]
100994337  RUNX3; runt related transcription factor 3 [KO:K09279]
100986750  HLA class II histocompatibility antigen, DRB1-4 beta chain [KO:K06752]
100987433  HLA class II histocompatibility antigen, DRB1-10 beta chain-like [KO:K06752]
100987081  HLA class II histocompatibility antigen, DR alpha chain [KO:K06752]
100967723  HLA class II histocompatibility antigen, DO alpha chain [KO:K06752]
100972641  HLA class II histocompatibility antigen, DQ beta 2 chain [KO:K06752]
100967376  RLA class II histocompatibility antigen, DP alpha-1 chain-like [KO:K06752]
100979649  HLA class II histocompatibility antigen, DQ alpha 2 chain-like [KO:K06752]
100968989  HLA class II histocompatibility antigen, DM alpha chain [KO:K06752]
100968410  MHC-DMB; HLA class II histocompatibility antigen, DM beta chain [KO:K06752]
100995577  HLA class II histocompatibility antigen, DP alpha 1 chain [KO:K06752]
100995226  Papa-DPB1; HLA class II histocompatibility antigen, DP beta 1 chain [KO:K06752]
100970847  HLA class II histocompatibility antigen, DO beta chain [KO:K06752]
100973583  HLA class II histocompatibility antigen, DQ alpha 2 chain [KO:K06752]
100972994  HLA class II histocompatibility antigen, DQ beta 1 chain [KO:K06752]
100993847  HLA class II histocompatibility antigen, DQ beta 1 chain-like [KO:K06752]
100993508  HLA class II histocompatibility antigen, DQ alpha 1 chain [KO:K06752]
100970574  CD4; CD4 molecule [KO:K06454]
100979670  LCK; LCK proto-oncogene, Src family tyrosine kinase [KO:K05856] [EC:2.7.10.2]
100978919  CD3E; CD3e molecule [KO:K06451]
100979261  CD3G; CD3g molecule [KO:K06452]
100975083  uncharacterized LOC100975083 [KO:K10785]
100985012  uncharacterized LOC100985012 [KO:K10785]
100988366  uncharacterized LOC100988366 [KO:K10785]
100982662  uncharacterized LOC100982662 [KO:K10785]
100983000  uncharacterized LOC100983000 [KO:K10785]
100995080  uncharacterized LOC100995080 [KO:K10785]
100988045  uncharacterized LOC100988045 [KO:K10785]
100972637  CD247; CD247 molecule [KO:K06453]
100979946  CD3D; CD3d molecule [KO:K06450]
100971372  ZAP70; zeta-chain (TCR) associated protein kinase 70kDa [KO:K07360] [EC:2.7.10.2]
100983902  LAT; linker for activation of T-cells [KO:K07362]
100995010  PLCG1; phospholipase C gamma 1 [KO:K01116] [EC:3.1.4.11]
100976987  PPP3CA; protein phosphatase 3 catalytic subunit alpha [KO:K04348] [EC:3.1.3.16]
100976831  PPP3CC; protein phosphatase 3 catalytic subunit gamma [KO:K04348] [EC:3.1.3.16]
100968593  PPP3CB; protein phosphatase 3 catalytic subunit beta [KO:K04348] [EC:3.1.3.16]
100995767  PPP3R2; protein phosphatase 3 regulatory subunit B, beta [KO:K06268]
100974281  NFATC1; nuclear factor of activated T-cells 1 [KO:K04446]
100980286  NFATC2; nuclear factor of activated T-cells 2 [KO:K17332]
100988212  NFATC3; nuclear factor of activated T-cells 3 [KO:K17333]
100995594  PRKCQ; protein kinase C theta [KO:K18052] [EC:2.7.11.13]
100995228  CHUK; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
100989390  IKBKB; inhibitor of nuclear factor kappa B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
100987483  IKBKG; inhibitor of nuclear factor kappa B kinase subunit gamma [KO:K07210]
100972867  NFKBIA; NFKB inhibitor alpha [KO:K04734]
100980612  NFKBIB; NFKB inhibitor beta [KO:K02581]
100975775  NFKBIE; NFKB inhibitor epsilon [KO:K05872]
100995567  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
100979542  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100987957  FOS; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379]
100982544  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
100983649  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
100980937  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
100981268  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
100990080  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
100984173  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
100982480  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
100980908  JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
100984780  IL2; interleukin 2 [KO:K05429]
100974407  IL2RA; interleukin 2 receptor subunit alpha [KO:K05068]
100992438  IL2RB; interleukin 2 receptor subunit beta [KO:K05069]
100986679  IL2RG; interleukin 2 receptor subunit gamma [KO:K05070]
100972035  JAK3; Janus kinase 3 [KO:K11218] [EC:2.7.10.2]
100988550  STAT5A; signal transducer and activator of transcription 5A [KO:K11223]
100989105  STAT5B; signal transducer and activator of transcription 5B [KO:K11224]
100988878  IL4; interleukin 4 [KO:K05430]
100969808  IL4R; interleukin 4 receptor [KO:K05071]
100989067  STAT6; signal transducer and activator of transcription 6 [KO:K11225]
100971194  GATA3; GATA binding protein 3 [KO:K17895]
100991249  IL5; interleukin 5 [KO:K05428]
100989787  IL13; interleukin 13 [KO:K05435]
100975910  MAF; MAF bZIP transcription factor [KO:K09035]
100984049  JAG1; jagged 1 [KO:K06052]
100991209  JAG2; jagged 2 [KO:K21635]
100973648  NOTCH1; notch 1 [KO:K02599]
100992229  NOTCH2; notch 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
pps04010  MAPK signaling pathway
pps04020  Calcium signaling pathway
pps04064  NF-kappa B signaling pathway
pps04330  Notch signaling pathway
pps04514  Cell adhesion molecules
pps04630  JAK-STAT signaling pathway
pps04660  T cell receptor signaling pathway
KO pathway
ko04658   

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