KEGG   PATHWAY: myd04658
Entry
myd04658                    Pathway                                
Name
Th1 and Th2 cell differentiation - Myotis davidii (David's myotis)
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
myd04658  Th1 and Th2 cell differentiation
myd04658

Other DBs
GO: 0045063 0045064
Organism
Myotis davidii (David's myotis) [GN:myd]
Gene
102758782  DLL1; delta like canonical Notch ligand 1 [KO:K06051]
102756052  DLL3; delta like canonical Notch ligand 3 [KO:K06051]
102752350  DLL4; delta like canonical Notch ligand 4 [KO:K06051]
102767944  NOTCH3; notch 3 [KO:K20995]
102753315  MAML3; mastermind like transcriptional coactivator 3 [KO:K06061]
102767217  MAML2; mastermind like transcriptional coactivator 2 [KO:K06061]
102754119  MAML1; mastermind like transcriptional coactivator 1 [KO:K06061]
102767994  RBPJL; recombination signal binding protein for immunoglobulin kappa J region like [KO:K06053]
102768470  RBPJ; recombination signal binding protein for immunoglobulin kappa J region [KO:K06053]
102770715  NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]
102770704  RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735]
102774208  IFNG; interferon gamma [KO:K04687]
102761556  IFNGR1; interferon gamma receptor 1 [KO:K05132]
102751646  IFNGR2; interferon gamma receptor 2 [KO:K05133]
102756517  JAK1; Janus kinase 1 [KO:K11217] [EC:2.7.10.2]
102768196  JAK2; Janus kinase 2 [KO:K04447] [EC:2.7.10.2]
102757059  STAT1; signal transducer and activator of transcription 1 [KO:K11220]
102753538  IL12A; interleukin 12A [KO:K05406]
102756968  IL12B; interleukin 12B [KO:K05425]
102769690  IL12RB1; interleukin 12 receptor subunit beta 1 [KO:K05063]
102751523  IL12RB2; interleukin 12 receptor subunit beta 2 [KO:K05064]
102751430  TYK2; tyrosine kinase 2 [KO:K11219] [EC:2.7.10.2]
102757535  STAT4; signal transducer and activator of transcription 4 [KO:K11222]
102755039  TBX21; T-box 21 [KO:K10166]
102753746  RUNX3; runt related transcription factor 3 [KO:K09279]
102762190  HLA class II histocompatibility antigen, DQ beta 1 chain-like [KO:K06752]
102774029  boLa class II histocompatibility antigen, DQB*0101 beta chain [KO:K06752]
102774320  HLA class II histocompatibility antigen, DQ alpha 2 chain [KO:K06752]
102751491  DLA class II histocompatibility antigen, DR-1 beta chain [KO:K06752]
102769789  HLA class II histocompatibility antigen, DQ beta 1 chain-like [KO:K06752]
102760150  H-2 class II histocompatibility antigen, E-S beta chain [KO:K06752]
102760441  HLA class II histocompatibility antigen, DRB1-16 beta chain [KO:K06752]
102760728  HLA class II histocompatibility antigen, DR beta 5 chain [KO:K06752]
102761022  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
102754620  HLA class II histocompatibility antigen, DQ alpha 1 chain-like [KO:K06752]
102754327  boLa class II histocompatibility antigen, DQB*0101 beta chain-like [KO:K06752]
102770854  HLA class II histocompatibility antigen, DQ beta 1 chain-like [KO:K06752]
102770559  SLA class II histocompatibility antigen, DQ haplotype D alpha chain [KO:K06752]
102764926  SLA class II histocompatibility antigen, DQ haplotype D alpha chain [KO:K06752]
102762831  HLA class II histocompatibility antigen, DRB1-4 beta chain-like [KO:K06752]
102762376  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
102762659  HLA class II histocompatibility antigen, DR beta 5 chain [KO:K06752]
102762934  DLA class II histocompatibility antigen, DR-1 beta chain [KO:K06752]
102767794  RLA class II histocompatibility antigen, DP alpha-1 chain-like [KO:K06752]
102768653  rano class II histocompatibility antigen, A beta chain [KO:K06752]
102768940  HLA class II histocompatibility antigen, DQ alpha 2 chain [KO:K06752]
102767515  HLA class II histocompatibility antigen, DP beta 1 chain [KO:K06752]
102753992  HLA class II histocompatibility antigen, DRB1-4 beta chain [KO:K06752]
102760947  HLA class II histocompatibility antigen, DM alpha chain [KO:K06752]
102761229  HLA class II histocompatibility antigen, DM beta chain [KO:K06752]
102755222  SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like [KO:K06752]
102761265  uncharacterized LOC102761265 [KO:K06752]
102760404  SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like [KO:K06752]
102760024  CD4; CD4 molecule [KO:K06454]
102764895  LCK; LCK proto-oncogene, Src family tyrosine kinase [KO:K05856] [EC:2.7.10.2]
102753033  CD3E; CD3e molecule [KO:K06451]
102753586  CD3G; CD3g molecule [KO:K06452]
107184444  uncharacterized LOC107184444 [KO:K10784]
102759035  T-cell receptor beta chain V region C5 [KO:K10785]
102756759  CD247; CD247 molecule [KO:K06453]
102753304  CD3D; CD3d molecule [KO:K06450]
102775001  ZAP70; tyrosine-protein kinase ZAP-70 [KO:K07360] [EC:2.7.10.2]
102762878  LAT; linker for activation of T-cells [KO:K07362]
102756475  PLCG1; phospholipase C gamma 1 [KO:K01116] [EC:3.1.4.11]
102755500  PPP3CA; protein phosphatase 3 catalytic subunit alpha [KO:K04348] [EC:3.1.3.16]
102753757  PPP3CC; protein phosphatase 3 catalytic subunit gamma [KO:K04348] [EC:3.1.3.16]
102754623  PPP3CB; protein phosphatase 3 catalytic subunit beta [KO:K04348] [EC:3.1.3.16]
102774846  PPP3R1; protein phosphatase 3 regulatory subunit B, alpha [KO:K06268]
102760712  PPP3R2; protein phosphatase 3 regulatory subunit B, beta [KO:K06268]
102763205  NFATC1; nuclear factor of activated T-cells 1 [KO:K04446]
102762996  NFATC2; nuclear factor of activated T-cells 2 [KO:K17332]
102765232  NFATC3; nuclear factor of activated T-cells 3 [KO:K17333]
102767625  PRKCQ; protein kinase C theta [KO:K18052] [EC:2.7.11.13]
102760888  CHUK; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
102773824  IKBKB; inhibitor of nuclear factor kappa B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
102772051  IKBKG; inhibitor of nuclear factor kappa B kinase subunit gamma [KO:K07210]
102763089  NFKBIA; NFKB inhibitor alpha [KO:K04734]
102768871  NFKBIB; NFKB inhibitor beta [KO:K02581]
102774530  NFKBIE; NFKB inhibitor epsilon [KO:K05872]
102769037  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102775211  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102764239  FOS; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379]
102770309  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
102770021  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
102755728  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
102756012  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
102772062  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
102764416  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
102775351  mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
107183844  JUNB; JunB proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
102752693  JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
102773629  IL2; interleukin 2 [KO:K05429]
102769642  IL2RA; interleukin 2 receptor subunit alpha [KO:K05068]
102768408  IL2RB; interleukin 2 receptor subunit beta [KO:K05069]
102757155  IL2RG; interleukin 2 receptor subunit gamma [KO:K05070]
102767426  JAK3; Janus kinase 3 [KO:K11218] [EC:2.7.10.2]
102762493  STAT5A; signal transducer and activator of transcription 5A [KO:K11223]
102773980  IL4; interleukin 4 [KO:K05430]
102752440  IL4R; interleukin 4 receptor [KO:K05071]
102768984  STAT6; signal transducer and activator of transcription 6 [KO:K11225]
102765057  GATA3; GATA binding protein 3 [KO:K17895]
102765865  IL5; interleukin 5 [KO:K05428]
102774264  IL13; interleukin 13 [KO:K05435]
102775187  MAF; MAF bZIP transcription factor [KO:K09035]
102754312  JAG1; jagged 1 [KO:K06052]
102759072  NOTCH1; notch 1 [KO:K02599]
102772197  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
myd04010  MAPK signaling pathway
myd04020  Calcium signaling pathway
myd04064  NF-kappa B signaling pathway
myd04330  Notch signaling pathway
myd04514  Cell adhesion molecules
myd04630  JAK-STAT signaling pathway
myd04660  T cell receptor signaling pathway
KO pathway
ko04658   
LinkDB

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