KEGG   PATHWAY: mcf04658
Entry
mcf04658                    Pathway                                
Name
Th1 and Th2 cell differentiation - Macaca fascicularis (crab-eating macaque)
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
mcf04658  Th1 and Th2 cell differentiation
mcf04658

Other DBs
GO: 0045063 0045064
Organism
Macaca fascicularis (crab-eating macaque) [GN:mcf]
Gene
102145271  DLL1; delta-like protein 1 [KO:K06051]
102125764  DLL4; delta-like protein 4 [KO:K06051]
102115332  DLL3; delta-like protein 3 isoform X1 [KO:K06051]
102120202  NOTCH3; neurogenic locus notch homolog protein 3 [KO:K20995]
102142627  MAML3; mastermind-like protein 3 [KO:K06061]
101866936  MAML1; mastermind-like protein 1 [KO:K06061]
102121017  MAML2; mastermind-like protein 2 isoform X1 [KO:K06061]
102141177  RBPJ; recombining binding protein suppressor of hairless isoform X1 [KO:K06053]
102120862  RBPJL; recombining binding protein suppressor of hairless-like protein isoform X1 [KO:K06053]
102138273  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
101867324  RELA; transcription factor p65 isoform X1 [KO:K04735]
102128291  IFNG; interferon gamma [KO:K04687]
101866179  IFNGR1; interferon gamma receptor 1 isoform X3 [KO:K05132]
102138221  IFNGR2; interferon gamma receptor 2 [KO:K05133]
102123983  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
102119008  JAK2; tyrosine-protein kinase JAK2 isoform X1 [KO:K04447] [EC:2.7.10.2]
101925134  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
102115316  IL12A; interleukin-12 subunit alpha [KO:K05406]
102124858  IL12B; interleukin-12 subunit beta [KO:K05425]
102143359  IL12RB1; interleukin-12 receptor subunit beta-1 isoform X1 [KO:K05063]
102131165  IL12RB2; interleukin-12 receptor subunit beta-2 [KO:K05064]
102143094  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
101925110  STAT4; signal transducer and activator of transcription 4 [KO:K11222]
102141237  TBX21; T-box transcription factor TBX21 [KO:K10166]
102140435  RUNX3; runt-related transcription factor 3 [KO:K09279]
102136468  HLA class II histocompatibility antigen, DP beta 1 chain isoform X1 [KO:K06752]
102137481  HLA class II histocompatibility antigen, DO alpha chain isoform X1 [KO:K06752]
102140649  HLA class II histocompatibility antigen, DM beta chain isoform X1 [KO:K06752]
102139994  HLA class II histocompatibility antigen, DM alpha chain isoform X1 [KO:K06752]
102145413  HLA class II histocompatibility antigen, DO beta chain [KO:K06752]
102132662  HLA class II histocompatibility antigen, DQ alpha 2 chain [KO:K06752]
102144414  HLA class II histocompatibility antigen, DR beta 5 chain isoform X1 [KO:K06752]
102144039  mamu class II histocompatibility antigen, DR alpha chain [KO:K06752]
102136862  HLA class II histocompatibility antigen, DP alpha 1 chain [KO:K06752]
102133044  HLA class II histocompatibility antigen, DQ beta 1 chain isoform X1 [KO:K06752]
123572852  H-2 class II histocompatibility antigen, A-D alpha chain-like [KO:K06752]
123572854  class II histocompatibility antigen, B-L beta chain-like [KO:K06752]
123572909  mamu class II histocompatibility antigen, DR alpha chain-like [KO:K06752]
101864991  CD4; T-cell surface glycoprotein CD4 [KO:K06454]
102140916  LCK; tyrosine-protein kinase Lck isoform X1 [KO:K05856] [EC:2.7.10.2]
102133065  CD3E; T-cell surface glycoprotein CD3 epsilon chain isoform X1 [KO:K06451]
102134381  CD3G; T-cell surface glycoprotein CD3 gamma chain isoform X1 [KO:K06452]
102118501  CD247; T-cell surface glycoprotein CD3 zeta chain isoform X1 [KO:K06453]
102133701  CD3D; T-cell surface glycoprotein CD3 delta chain isoform X3 [KO:K06450]
102135442  tyrosine-protein kinase ZAP-70 [KO:K07360] [EC:2.7.10.2]
102143768  LAT; linker for activation of T-cells family member 1 isoform X1 [KO:K07362]
102138726  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
101926738  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
102134477  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
101866070  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
102137250  PPP3R1; calcineurin subunit B type 1 isoform X1 [KO:K06268]
101866439  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
102133233  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
102136960  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
102136724  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
102125438  PRKCQ; protein kinase C theta type [KO:K18052] [EC:2.7.11.13]
102115964  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
102146604  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X2 [KO:K07209] [EC:2.7.11.10]
102115368  IKBKG; NF-kappa-B essential modulator isoform X5 [KO:K07210]
101867458  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
102130059  NFKBIB; NF-kappa-B inhibitor beta isoform X2 [KO:K02581]
102130086  NFKBIE; NF-kappa-B inhibitor epsilon [KO:K05872]
102145011  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102116996  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
102143716  FOS; proto-oncogene c-Fos [KO:K04379]
101867352  MAPK13; mitogen-activated protein kinase 13 isoform X2 [KO:K04441] [EC:2.7.11.24]
101926770  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
102134421  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
101867305  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
102118497  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
102126339  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
102121272  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
102126446  JUN; transcription factor AP-1 [KO:K04448]
102129830  IL2; interleukin-2 [KO:K05429]
102123605  IL2RA; interleukin-2 receptor subunit alpha isoform X1 [KO:K05068]
102138714  IL2RB; interleukin-2 receptor subunit beta isoform X1 [KO:K05069]
102144912  IL2RG; cytokine receptor common subunit gamma [KO:K05070]
102134669  JAK3; tyrosine-protein kinase JAK3 isoform X1 [KO:K11218] [EC:2.7.10.2]
102120556  signal transducer and activator of transcription 5A [KO:K11223]
102127060  signal transducer and activator of transcription 5B [KO:K11224]
107130068  IL4; interleukin-4 [KO:K05430]
102133649  IL4R; interleukin-4 receptor subunit alpha isoform X1 [KO:K05071]
102117594  STAT6; signal transducer and activator of transcription 6 isoform X1 [KO:K11225]
102135253  GATA3; trans-acting T-cell-specific transcription factor GATA-3 isoform X1 [KO:K17895]
102125522  IL5; interleukin-5 [KO:K05428]
102125887  IL13; interleukin-13 [KO:K05435]
102120730  MAF; transcription factor Maf isoform X1 [KO:K09035]
102132875  JAG1; protein jagged-1 isoform X1 [KO:K06052]
102119283  JAG2; protein jagged-2 isoform X1 [KO:K21635]
102138307  NOTCH1; neurogenic locus notch homolog protein 1 isoform X1 [KO:K02599]
101864989  NOTCH2; neurogenic locus notch homolog protein 2 isoform X1 [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
mcf04010  MAPK signaling pathway
mcf04020  Calcium signaling pathway
mcf04064  NF-kappa B signaling pathway
mcf04330  Notch signaling pathway
mcf04514  Cell adhesion molecules
mcf04630  JAK-STAT signaling pathway
mcf04660  T cell receptor signaling pathway
KO pathway
ko04658   
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