KEGG   PATHWAY: mun04658
Entry
mun04658                    Pathway                                
Name
Th1 and Th2 cell differentiation - Meriones unguiculatus (Mongolian gerbil)
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
mun04658  Th1 and Th2 cell differentiation
mun04658

Other DBs
GO: 0045063 0045064
Organism
Meriones unguiculatus (Mongolian gerbil) [GN:mun]
Gene
110561125  Dll1; delta-like protein 1 [KO:K06051]
110564728  Dll3; delta-like protein 3 [KO:K06051]
110550579  Dll4; delta-like protein 4 [KO:K06051]
110559877  Notch3; neurogenic locus notch homolog protein 3 isoform X1 [KO:K20995]
110557393  Maml1; mastermind-like protein 1 [KO:K06061]
110554036  Maml2; mastermind-like protein 2 isoform X1 [KO:K06061]
110549424  Maml3; mastermind-like protein 3 [KO:K06061]
110552767  Rbpj; recombining binding protein suppressor of hairless isoform X1 [KO:K06053]
110563390  Rbpjl; recombining binding protein suppressor of hairless-like protein isoform X2 [KO:K06053]
110558602  Nfkb1; nuclear factor NF-kappa-B p105 subunit isoform X2 [KO:K02580]
110549347  Rela; transcription factor p65 isoform X1 [KO:K04735]
110561827  Ifng; interferon gamma [KO:K04687]
110557641  Ifngr1; interferon gamma receptor 1 [KO:K05132]
110541673  Ifngr2; interferon gamma receptor 2 [KO:K05133]
110555551  Jak1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
110547004  Jak2; tyrosine-protein kinase JAK2 [KO:K04447] [EC:2.7.10.2]
110552020  Stat1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
110557307  Il12a; interleukin-12 subunit alpha [KO:K05406]
110548438  Il12b; interleukin-12 subunit beta [KO:K05425]
110549207  Il12rb1; interleukin-12 receptor subunit beta-1 isoform X1 [KO:K05063]
110555653  Il12rb2; interleukin-12 receptor subunit beta-2 isoform X1 [KO:K05064]
110555765  Tyk2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
110552026  Stat4; signal transducer and activator of transcription 4 [KO:K11222]
110551430  Tbx21; T-box transcription factor TBX21 [KO:K10166]
110564924  Runx3; runt-related transcription factor 3 [KO:K09279]
110543060  class II histocompatibility antigen, M alpha chain [KO:K06752]
110543088  class II histocompatibility antigen, M beta 1 chain isoform X1 [KO:K06752]
110543117  H-2 class II histocompatibility antigen, E-D beta chain-like isoform X1 [KO:K06752]
110543181  HLA class II histocompatibility antigen, DO alpha chain [KO:K06752]
110543223  H-2 class II histocompatibility antigen, I-E beta chain-like [KO:K06752]
110543234  rano class II histocompatibility antigen, B-1 beta chain-like [KO:K06752]
110543301  HLA class II histocompatibility antigen, DP beta 1 chain-like isoform X2 [KO:K06752]
110543331  RLA class II histocompatibility antigen, DP alpha-1 chain isoform X1 [KO:K06752]
110544088  H-2 class II histocompatibility antigen, A-F alpha chain [KO:K06752]
110542965  HLA class II histocompatibility antigen, DO beta chain isoform X2 [KO:K06752]
110543034  H-2 class II histocompatibility antigen, E-U alpha chain-like [KO:K06752]
110548574  Cd4; T-cell surface glycoprotein CD4 isoform X1 [KO:K06454]
110548547  Lck; tyrosine-protein kinase Lck [KO:K05856] [EC:2.7.10.2]
110549111  T-cell surface glycoprotein CD3 epsilon chain [KO:K06451]
110549119  T-cell surface glycoprotein CD3 gamma chain [KO:K06452]
110562425  Cd247; T-cell surface glycoprotein CD3 zeta chain isoform X1 [KO:K06453]
110549118  T-cell surface glycoprotein CD3 delta chain [KO:K06450]
110545437  tyrosine-protein kinase ZAP-70 [KO:K07360] [EC:2.7.10.2]
110548013  Lat; linker for activation of T-cells family member 1 isoform X1 [KO:K07362]
110552794  Plcg1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
110555973  Ppp3ca; protein phosphatase 3 catalytic subunit alpha isoform X1 [KO:K04348] [EC:3.1.3.16]
110551992  Ppp3cb; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X4 [KO:K04348] [EC:3.1.3.16]
110551668  Ppp3cc; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X2 [KO:K04348] [EC:3.1.3.16]
110558957  Ppp3r1; calcineurin subunit B type 1 [KO:K06268]
110561325  Ppp3r2; calcineurin subunit B type 2 [KO:K06268]
110550273  Nfatc1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
110547352  Nfatc2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
110545902  Nfatc3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
110556894  Prkcq; protein kinase C theta type [KO:K18052] [EC:2.7.11.13]
110552966  Chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
110544653  LOW QUALITY PROTEIN: inhibitor of nuclear factor kappa-B kinase subunit alpha-like [KO:K04467] [EC:2.7.11.10]
110556613  Ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
110562528  Ikbkg; NF-kappa-B essential modulator isoform X3 [KO:K07210]
110562401  Nfkbia; NF-kappa-B inhibitor alpha [KO:K04734]
110552558  Nfkbib; NF-kappa-B inhibitor beta isoform X1 [KO:K02581]
110555836  Nfkbie; NF-kappa-B inhibitor epsilon isoform X1 [KO:K05872]
110553796  Mapk1; mitogen-activated protein kinase 1 isoform X2 [KO:K04371] [EC:2.7.11.24]
110547978  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
110546962  Fos; protein c-Fos [KO:K04379]
110546562  Mapk14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
110546585  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
110549680  Mapk11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
110549673  Mapk12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
110552285  Mapk8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
110557386  Mapk9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
110562875  Mapk10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
110559727  Jun; transcription factor Jun [KO:K04448]
110545874  Il2; interleukin-2 [KO:K05429]
110560079  interleukin-2-like [KO:K05429]
110556899  Il2ra; interleukin-2 receptor subunit alpha [KO:K05068]
110548465  Il2rb; interleukin-2 receptor subunit beta [KO:K05069]
110564656  Il2rg; cytokine receptor common subunit gamma [KO:K05070]
110549202  Jak3; tyrosine-protein kinase JAK3 [KO:K11218] [EC:2.7.10.2]
110550874  signal transducer and activator of transcription 5A [KO:K11223]
110550889  signal transducer and activator of transcription 5B isoform X1 [KO:K11224]
110548759  Il4; interleukin-4 [KO:K05430]
110564641  Il4r; interleukin-4 receptor subunit alpha isoform X1 [KO:K05071]
110561573  Stat6; signal transducer and activator of transcription 6 isoform X2 [KO:K11225]
110545620  Gata3; trans-acting T-cell-specific transcription factor GATA-3 isoform X2 [KO:K17895]
110548757  Il5; interleukin-5 [KO:K05428]
110548783  Il13; interleukin-13 [KO:K05435]
110551463  Maf; transcription factor Maf isoform X1 [KO:K09035]
110565314  Jag1; protein jagged-1 [KO:K06052]
110559689  Jag2; protein jagged-2 isoform X1 [KO:K21635]
110550836  Notch1; neurogenic locus notch homolog protein 1 [KO:K02599]
110545909  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
mun04010  MAPK signaling pathway
mun04020  Calcium signaling pathway
mun04064  NF-kappa B signaling pathway
mun04330  Notch signaling pathway
mun04514  Cell adhesion molecules
mun04630  JAK-STAT signaling pathway
mun04660  T cell receptor signaling pathway
KO pathway
ko04658   
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