KEGG   PATHWAY: vlg04658
Entry
vlg04658                    Pathway                                
Name
Th1 and Th2 cell differentiation - Vulpes lagopus (Arctic fox)
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
vlg04658  Th1 and Th2 cell differentiation
vlg04658

Other DBs
GO: 0045063 0045064
Organism
Vulpes lagopus (Arctic fox) [GN:vlg]
Gene
121473270  DLL1; delta-like protein 1 [KO:K06051]
121485209  DLL3; delta-like protein 3 [KO:K06051]
121485429  DLL4; delta-like protein 4 [KO:K06051]
121495306  NOTCH3; neurogenic locus notch homolog protein 3 [KO:K20995]
121476587  MAML2; mastermind-like protein 2 isoform X1 [KO:K06061]
121492865  MAML3; mastermind-like protein 3 isoform X1 [KO:K06061]
121494333  MAML1; mastermind-like protein 1 [KO:K06061]
121489096  RBPJ; recombining binding protein suppressor of hairless isoform X1 [KO:K06053]
121477726  RBPJL; recombining binding protein suppressor of hairless-like protein [KO:K06053]
121492781  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
121471268  RELA; transcription factor p65 isoform X1 [KO:K04735]
121491993  IFNG; interferon gamma [KO:K04687]
121485259  IFNGR1; interferon gamma receptor 1 [KO:K05132]
121479429  IFNGR2; interferon gamma receptor 2 isoform X1 [KO:K05133]
121499401  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
121483167  JAK2; tyrosine-protein kinase JAK2 isoform X1 [KO:K04447] [EC:2.7.10.2]
121480638  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
121477529  IL12A; interleukin-12 subunit alpha [KO:K05406]
121486324  IL12B; interleukin-12 subunit beta [KO:K05425]
121495556  IL12RB1; interleukin-12 receptor subunit beta-1 isoform X1 [KO:K05063]
121499494  IL12RB2; interleukin-12 receptor subunit beta-2 isoform X1 [KO:K05064]
121495696  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
121480498  STAT4; signal transducer and activator of transcription 4 isoform X1 [KO:K11222]
121472759  TBX21; T-box transcription factor TBX21 [KO:K10166]
121498221  RUNX3; runt-related transcription factor 3 [KO:K09279]
121473937  HLA class II histocompatibility antigen, DR alpha chain [KO:K06752]
121474464  SLA class II histocompatibility antigen, DQ haplotype C beta chain-like [KO:K06752]
121471276  SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like [KO:K06752]
121471845  RLA class II histocompatibility antigen, DP alpha-1 chain [KO:K06752]
121486869  LOW QUALITY PROTEIN: HLA class II histocompatibility antigen, DP beta 1 chain [KO:K06752]
121498409  HLA class II histocompatibility antigen, DM alpha chain isoform X1 [KO:K06752]
121498441  HLA class II histocompatibility antigen, DO alpha chain [KO:K06752]
121499713  DLA class II histocompatibility antigen, DR-1 beta chain [KO:K06752]
121501638  HLA class II histocompatibility antigen, DM beta chain [KO:K06752]
121494772  HLA class II histocompatibility antigen, DO beta chain-like [KO:K06752]
121479658  CD4; T-cell surface glycoprotein CD4 [KO:K06454]
121497458  LCK; tyrosine-protein kinase Lck isoform X1 [KO:K05856] [EC:2.7.10.2]
121499400  CD3E; T-cell surface glycoprotein CD3 epsilon chain [KO:K06451]
121500171  CD3G; T-cell surface glycoprotein CD3 gamma chain [KO:K06452]
121472894  CD247; T-cell surface glycoprotein CD3 zeta chain [KO:K06453]
121500522  CD3D; T-cell surface glycoprotein CD3 delta chain [KO:K06450]
121491045  tyrosine-protein kinase ZAP-70 [KO:K07360] [EC:2.7.10.2]
121486346  LAT; linker for activation of T-cells family member 1 isoform X1 [KO:K07362]
121477887  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
121488319  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
121497400  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
121493459  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
121490871  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
121495449  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
121481950  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
121478169  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
121499454  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
121498013  PRKCQ; protein kinase C theta type [KO:K18052] [EC:2.7.11.13]
121484113  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
121489510  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
121482779  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
121493914  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
121484250  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
121493724  NFKBIE; NF-kappa-B inhibitor epsilon [KO:K05872]
121475510  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
121486545  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
121493811  FOS; proto-oncogene c-Fos [KO:K04379]
121482054  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
121485950  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
121491672  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
121491673  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
121482830  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
121493739  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
121494640  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
121500205  JUN; transcription factor AP-1 [KO:K04448]
121492803  IL2; interleukin-2 [KO:K05429]
121496900  IL2RA; interleukin-2 receptor subunit alpha isoform X1 [KO:K05068]
121490488  IL2RB; interleukin-2 receptor subunit beta isoform X1 [KO:K05069]
121483086  IL2RG; cytokine receptor common subunit gamma isoform X1 [KO:K05070]
121494166  JAK3; tyrosine-protein kinase JAK3 [KO:K11218] [EC:2.7.10.2]
121473588  signal transducer and activator of transcription 5A [KO:K11223]
121472926  STAT5B; signal transducer and activator of transcription 5B isoform X1 [KO:K11224]
121496081  IL4; interleukin-4 [KO:K05430]
121487679  IL4R; interleukin-4 receptor subunit alpha isoform X1 [KO:K05071]
121490605  STAT6; signal transducer and activator of transcription 6 [KO:K11225]
121498138  GATA3; LOW QUALITY PROTEIN: trans-acting T-cell-specific transcription factor GATA-3 [KO:K17895]
121494387  IL5; interleukin-5 [KO:K05428]
121495939  IL13; interleukin-13 isoform X1 [KO:K05435]
121499722  MAF; transcription factor Maf [KO:K09035]
121478025  JAG1; protein jagged-1 isoform X1 [KO:K06052]
121493529  JAG2; protein jagged-2 isoform X1 [KO:K21635]
121472943  NOTCH1; neurogenic locus notch homolog protein 1 [KO:K02599]
121490555  NOTCH2; neurogenic locus notch homolog protein 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
vlg04010  MAPK signaling pathway
vlg04020  Calcium signaling pathway
vlg04064  NF-kappa B signaling pathway
vlg04330  Notch signaling pathway
vlg04514  Cell adhesion molecules
vlg04630  JAK-STAT signaling pathway
vlg04660  T cell receptor signaling pathway
KO pathway
ko04658   
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