KEGG   PATHWAY: oda04658
Entry
oda04658                    Pathway                                
Name
Th1 and Th2 cell differentiation - Oryx dammah (scimitar-horned oryx)
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
oda04658  Th1 and Th2 cell differentiation
oda04658

Other DBs
GO: 0045063 0045064
Organism
Oryx dammah (scimitar-horned oryx) [GN:oda]
Gene
120853192  DLL4; delta-like protein 4 [KO:K06051]
120862926  DLL1; delta-like protein 1 [KO:K06051]
120872395  DLL3; delta-like protein 3 [KO:K06051]
120864149  NOTCH3; neurogenic locus notch homolog protein 3 [KO:K20995]
120876183  MAML2; mastermind-like protein 2 [KO:K06061]
120870906  MAML3; mastermind-like protein 3 [KO:K06061]
120864347  MAML1; mastermind-like protein 1 [KO:K06061]
120869544  RBPJL; recombining binding protein suppressor of hairless-like protein [KO:K06053]
120862003  RBPJ; recombining binding protein suppressor of hairless isoform X1 [KO:K06053]
120861869  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
120874649  RELA; transcription factor p65 [KO:K04735]
120857709  IFNG; interferon gamma [KO:K04687]
120863075  IFNGR1; interferon gamma receptor 1 isoform X1 [KO:K05132]
120854372  IFNGR2; interferon gamma receptor 2 [KO:K05133]
120857038  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
120860228  tyrosine-protein kinase JAK2-like isoform X1 [KO:K04447] [EC:2.7.10.2]
120865363  JAK2; tyrosine-protein kinase JAK2 isoform X1 [KO:K04447] [EC:2.7.10.2]
120854684  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
120881582  IL12A; LOW QUALITY PROTEIN: interleukin-12 subunit alpha [KO:K05406]
120863361  IL12B; interleukin-12 subunit beta [KO:K05425]
120864211  IL12RB1; interleukin-12 receptor subunit beta-1 isoform X1 [KO:K05063]
120856565  IL12RB2; interleukin-12 receptor subunit beta-2 [KO:K05064]
120863977  TYK2; non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
120854683  STAT4; signal transducer and activator of transcription 4 [KO:K11222]
120867262  TBX21; T-box transcription factor TBX21 [KO:K10166]
120855053  RUNX3; runt-related transcription factor 3 [KO:K09279]
120859624  BOLA class I histocompatibility antigen, alpha chain BL3-7-like [KO:K06752]
120860003  BOLA class I histocompatibility antigen, alpha chain BL3-7-like [KO:K06752]
120860570  SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like [KO:K06752]
120869766  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
120869857  HLA class II histocompatibility antigen, DM alpha chain [KO:K06752]
120869858  HLA class II histocompatibility antigen, DO alpha chain-like [KO:K06752]
120869859  HLA class II histocompatibility antigen, DM beta chain [KO:K06752]
120869865  HLA class II histocompatibility antigen, DO beta chain isoform X1 [KO:K06752]
120869866  rano class II histocompatibility antigen, A beta chain-like [KO:K06752]
120869867  SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like [KO:K06752]
120869868  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
120870613  mamu class II histocompatibility antigen, DR alpha chain [KO:K06752]
120870614  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
120870615  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
120870618  boLa class II histocompatibility antigen, DQB*0101 beta chain isoform X1 [KO:K06752]
120870619  SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like [KO:K06752]
120870620  HLA class II histocompatibility antigen, DQ alpha 2 chain-like [KO:K06752]
120870621  boLa class II histocompatibility antigen, DQB*0101 beta chain-like [KO:K06752]
120858732  CD4; T-cell surface glycoprotein CD4 [KO:K06454]
120854212  LCK; tyrosine-protein kinase Lck [KO:K05856] [EC:2.7.10.2]
120876318  CD3E; T-cell surface glycoprotein CD3 epsilon chain [KO:K06451]
120876319  CD3G; T-cell surface glycoprotein CD3 gamma chain [KO:K06452]
120855485  CD247; T-cell surface glycoprotein CD3 zeta chain isoform X1 [KO:K06453]
120876320  CD3D; T-cell surface glycoprotein CD3 delta chain [KO:K06450]
120883562  tyrosine-protein kinase ZAP-70 [KO:K07360] [EC:2.7.10.2]
120877128  LAT; linker for activation of T-cells family member 1 isoform X1 [KO:K07362]
120869330  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
120861873  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
120865288  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
120865483  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
120851376  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
120864045  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
120880955  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
120869072  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
120872701  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
120869142  PRKCQ; protein kinase C theta type [KO:K18052] [EC:2.7.11.13]
120873530  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
120865846  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
120881825  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
120875083  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
120872421  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
120870082  NFKBIE; NF-kappa-B inhibitor epsilon [KO:K05872]
120882996  mitogen-activated protein kinase 1-like [KO:K04371] [EC:2.7.11.24]
120876943  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
120871418  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
120852702  FOS; proto-oncogene c-Fos [KO:K04379]
120870210  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
120870211  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
120857807  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
120857808  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
120861535  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
120864358  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
120865345  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
120857086  JUN; transcription factor AP-1 [KO:K04448]
120870984  IL2; interleukin-2 [KO:K05429]
120869146  IL2RA; interleukin-2 receptor subunit alpha [KO:K05068]
120861184  interleukin-2 receptor subunit beta-like [KO:K05069]
120858560  interleukin-2 receptor subunit beta-like [KO:K05069]
120882006  IL2RG; cytokine receptor common subunit gamma [KO:K05070]
120864206  JAK3; tyrosine-protein kinase JAK3 [KO:K11218] [EC:2.7.10.2]
120867072  signal transducer and activator of transcription 5A isoform X1 [KO:K11223]
120867075  signal transducer and activator of transcription 5B isoform X1 [KO:K11224]
120864752  IL4; interleukin-4 [KO:K05430]
120876403  IL4R; interleukin-4 receptor subunit alpha isoform X1 [KO:K05071]
120857477  STAT6; signal transducer and activator of transcription 6 isoform X1 [KO:K11225]
120869130  GATA3; trans-acting T-cell-specific transcription factor GATA-3 isoform X1 [KO:K17895]
120864746  IL5; interleukin-5 [KO:K05428]
120864748  IL13; interleukin-13 [KO:K05435]
120873340  MAF; transcription factor Maf [KO:K09035]
120869179  JAG1; protein jagged-1 [KO:K06052]
120875672  JAG2; protein jagged-2 [KO:K21635]
120852153  NOTCH1; neurogenic locus notch homolog protein 1 [KO:K02599]
120855992  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
oda04010  MAPK signaling pathway
oda04020  Calcium signaling pathway
oda04064  NF-kappa B signaling pathway
oda04330  Notch signaling pathway
oda04514  Cell adhesion molecules
oda04630  JAK-STAT signaling pathway
oda04660  T cell receptor signaling pathway
KO pathway
ko04658   
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