KEGG   PATHWAY: myb04658
Entry
myb04658                    Pathway                                
Name
Th1 and Th2 cell differentiation - Myotis brandtii (Brandt's bat)
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
myb04658  Th1 and Th2 cell differentiation
myb04658

Other DBs
GO: 0045063 0045064
Organism
Myotis brandtii (Brandt's bat) [GN:myb]
Gene
102257976  DLL4; delta like canonical Notch ligand 4 [KO:K06051]
102241481  DLL1; delta like canonical Notch ligand 1 [KO:K06051]
102242880  DLL3; delta like canonical Notch ligand 3 [KO:K06051]
102263849  NOTCH3; notch 3 [KO:K20995]
102242544  MAML1; mastermind like transcriptional coactivator 1 [KO:K06061]
102248464  MAML2; mastermind like transcriptional coactivator 2 [KO:K06061]
102259937  MAML3; mastermind like transcriptional coactivator 3 [KO:K06061]
102251519  RBPJL; recombination signal binding protein for immunoglobulin kappa J region like [KO:K06053]
102247977  RBPJ; recombination signal binding protein for immunoglobulin kappa J region [KO:K06053]
102255251  NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]
102263790  RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735]
102254028  IFNG; interferon gamma [KO:K04687]
102258073  IFNGR1; interferon gamma receptor 1 [KO:K05132]
102260069  IFNGR2; interferon gamma receptor 2 [KO:K05133]
102260801  JAK1; Janus kinase 1 [KO:K11217] [EC:2.7.10.2]
102253056  JAK2; Janus kinase 2 [KO:K04447] [EC:2.7.10.2]
102243651  STAT1; signal transducer and activator of transcription 1 [KO:K11220]
102251395  IL12A; interleukin 12A [KO:K05406]
102253394  IL12B; interleukin 12B [KO:K05425]
102253710  IL12RB1; interleukin 12 receptor subunit beta 1 [KO:K05063]
102240232  IL12RB2; interleukin 12 receptor subunit beta 2 [KO:K05064]
102244385  TYK2; tyrosine kinase 2 [KO:K11219] [EC:2.7.10.2]
102244347  STAT4; signal transducer and activator of transcription 4 [KO:K11222]
102252074  TBX21; T-box 21 [KO:K10166]
102248546  RUNX3; runt related transcription factor 3 [KO:K09279]
102252603  HLA class II histocompatibility antigen, DP beta 1 chain [KO:K06752]
102242640  H-2 class II histocompatibility antigen, E-S beta chain [KO:K06752]
102241033  DLA class II histocompatibility antigen, DR-1 beta chain [KO:K06752]
102241645  DLA class II histocompatibility antigen, DR-1 beta chain [KO:K06752]
102242559  HLA class II histocompatibility antigen, DRB1-1 beta chain [KO:K06752]
102242249  HLA class II histocompatibility antigen, DRB1-4 beta chain [KO:K06752]
102263678  HLA class II histocompatibility antigen, DQ beta 1 chain [KO:K06752]
102255852  SLA class II histocompatibility antigen, DQ haplotype D alpha chain [KO:K06752]
102256158  HLA class II histocompatibility antigen, DQ beta 1 chain [KO:K06752]
102251097  SLA class II histocompatibility antigen, DQ haplotype D alpha chain [KO:K06752]
102250801  HLA class II histocompatibility antigen, DQ beta 1 chain [KO:K06752]
102242568  SLA class II histocompatibility antigen, DQ haplotype D beta chain [KO:K06752]
102242876  HLA class II histocompatibility antigen, DQ alpha 2 chain [KO:K06752]
102259226  boLa class II histocompatibility antigen, DQB*0101 beta chain-like [KO:K06752]
102249039  H-2 class II histocompatibility antigen, A-U alpha chain [KO:K06752]
102263829  HLA class II histocompatibility antigen, DR alpha chain [KO:K06752]
102245034  DLA class II histocompatibility antigen, DR-1 beta chain [KO:K06752]
102259410  HLA class II histocompatibility antigen, DRB1-4 beta chain-like [KO:K06752]
102249578  boLa class II histocompatibility antigen, DQB*0101 beta chain [KO:K06752]
102252319  RLA class II histocompatibility antigen, DP alpha-1 chain-like [KO:K06752]
102251129  HLA class II histocompatibility antigen, DQ alpha 2 chain [KO:K06752]
102251414  SLA class II histocompatibility antigen, DQ haplotype C beta chain-like [KO:K06752]
102244632  SLA class II histocompatibility antigen, DQ haplotype C beta chain-like [KO:K06752]
102245825  HLA class II histocompatibility antigen, DM beta chain [KO:K06752]
102246131  HLA class II histocompatibility antigen, DM alpha chain [KO:K06752]
102262721  CD4; CD4 molecule [KO:K06454]
102242493  LCK; LCK proto-oncogene, Src family tyrosine kinase [KO:K05856] [EC:2.7.10.2]
102240865  CD3E; CD3e molecule [KO:K06451]
102240258  CD3G; CD3g molecule [KO:K06452]
102256861  CD247; CD247 molecule [KO:K06453]
102240563  CD3D; CD3d molecule [KO:K06450]
102259670  ZAP70; zeta-chain (TCR) associated protein kinase 70kDa [KO:K07360] [EC:2.7.10.2]
102261789  LAT; linker for activation of T-cells [KO:K07362]
102248243  PLCG1; phospholipase C gamma 1 [KO:K01116] [EC:3.1.4.11]
102264111  PPP3CC; protein phosphatase 3 catalytic subunit gamma [KO:K04348] [EC:3.1.3.16]
102251300  PPP3CB; protein phosphatase 3 catalytic subunit beta [KO:K04348] [EC:3.1.3.16]
102245752  PPP3CA; protein phosphatase 3 catalytic subunit alpha [KO:K04348] [EC:3.1.3.16]
102250711  PPP3R1; protein phosphatase 3 regulatory subunit B, alpha [KO:K06268]
102247129  PPP3R2; protein phosphatase 3 regulatory subunit B, beta [KO:K06268]
102245976  NFATC1; nuclear factor of activated T-cells 1 [KO:K04446]
102246844  NFATC2; nuclear factor of activated T-cells 2 [KO:K17332]
102249455  NFATC3; nuclear factor of activated T-cells 3 [KO:K17333]
102242050  PRKCQ; protein kinase C theta [KO:K18052] [EC:2.7.11.13]
102261467  CHUK; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
102261405  IKBKB; inhibitor of nuclear factor kappa B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
102252013  IKBKG; inhibitor of nuclear factor kappa B kinase subunit gamma [KO:K07210]
102256580  NFKBIA; NFKB inhibitor alpha [KO:K04734]
102261181  NFKBIB; NFKB inhibitor beta [KO:K02581]
102253454  NFKBIE; NFKB inhibitor epsilon [KO:K05872]
102255250  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102245641  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102246307  FOS; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379]
102254628  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
102248097  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
102254920  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
106723559  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
102259984  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
102263026  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
102246292  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
102260808  JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
102246940  IL2; interleukin 2 [KO:K05429]
102249529  IL2RA; interleukin 2 receptor subunit alpha [KO:K05068]
102241115  IL2RB; interleukin 2 receptor subunit beta [KO:K05069]
102241164  IL2RG; interleukin 2 receptor subunit gamma [KO:K05070]
102241153  JAK3; Janus kinase 3 [KO:K11218] [EC:2.7.10.2]
102240764  STAT5A; signal transducer and activator of transcription 5A [KO:K11223]
102241062  STAT5B; signal transducer and activator of transcription 5B [KO:K11224]
102243627  IL4; interleukin 4 [KO:K05430]
102243995  interleukin-4 receptor subunit alpha [KO:K05071]
102251654  STAT6; signal transducer and activator of transcription 6 [KO:K11225]
102245610  GATA3; GATA binding protein 3 [KO:K17895]
102243165  IL5; interleukin 5 [KO:K05428]
102243347  IL13; interleukin 13 [KO:K05435]
102253258  MAF; MAF bZIP transcription factor [KO:K09035]
102239114  JAG1; jagged 1 [KO:K06052]
102253740  NOTCH2; notch 2 [KO:K20994]
Compound
C00076  Calcium cation
C00165  Diacylglycerol
C01245  D-myo-Inositol 1,4,5-trisphosphate
Reference
PMID:19375293
  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
PMID:22044277
  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
PMID:11752608
  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
PMID:11121747
  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
PMID:23624818
  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
PMID:23405903
  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
PMID:20969597
  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
PMID:19151746
  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
PMID:15819694
  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
PMID:24113868
  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
PMID:12171942
  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
PMID:19362457
  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
PMID:20065998
  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
PMID:26044597
  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
PMID:19151747
  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
PMID:19165228
  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
PMID:23336087
  Authors
Pahan K, Mondal S
  Title
Crosstalk between Nitric Oxide and T helper cells.
  Journal
J Clin Cell Immunol 3:e109 (2012)
Reference
PMID:22566933
  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
myb04010  MAPK signaling pathway
myb04020  Calcium signaling pathway
myb04064  NF-kappa B signaling pathway
myb04330  Notch signaling pathway
myb04514  Cell adhesion molecules
myb04630  JAK-STAT signaling pathway
myb04660  T cell receptor signaling pathway
KO pathway
ko04658   
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