KEGG   PATHWAY: pcad04658
Entry
pcad04658                   Pathway                                
Name
Th1 and Th2 cell differentiation - Physeter catodon (sperm whale)
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
pcad04658  Th1 and Th2 cell differentiation
pcad04658

Other DBs
GO: 0045063 0045064
Organism
Physeter catodon (sperm whale) [GN:pcad]
Gene
102978082  DLL1; delta-like protein 1 isoform X1 [KO:K06051]
102993790  DLL4; delta-like protein 4 [KO:K06051]
102994639  DLL3; delta-like protein 3 [KO:K06051]
102974641  NOTCH3; neurogenic locus notch homolog protein 3 isoform X2 [KO:K20995]
102987479  MAML2; mastermind-like protein 2 [KO:K06061]
102986756  MAML1; mastermind-like protein 1 [KO:K06061]
102988559  MAML3; mastermind-like protein 3 isoform X1 [KO:K06061]
102980498  recombining binding protein suppressor of hairless isoform X1 [KO:K06053]
102989584  RBPJL; recombining binding protein suppressor of hairless-like protein isoform X1 [KO:K06053]
102996082  LOW QUALITY PROTEIN: recombining binding protein suppressor of hairless-like [KO:K06053]
102981135  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
102974198  RELA; transcription factor p65 isoform X1 [KO:K04735]
102981551  IFNG; interferon gamma [KO:K04687]
102977921  IFNGR1; interferon gamma receptor 1 [KO:K05132]
102997040  IFNGR2; interferon gamma receptor 2 isoform X2 [KO:K05133]
102988182  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
102978811  JAK2; tyrosine-protein kinase JAK2 isoform X2 [KO:K04447] [EC:2.7.10.2]
102977655  STAT1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
102982335  IL12A; interleukin-12 subunit alpha [KO:K05406]
102980587  IL12B; interleukin-12 subunit beta [KO:K05425]
102991223  IL12RB1; interleukin-12 receptor subunit beta-1 isoform X2 [KO:K05063]
102991572  interleukin-12 receptor subunit beta-2 [KO:K05064]
102985137  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
102977366  STAT4; signal transducer and activator of transcription 4 [KO:K11222]
102995274  TBX21; T-box transcription factor TBX21 [KO:K10166]
102991197  RUNX3; runt-related transcription factor 3 isoform X2 [KO:K09279]
102994322  HLA class II histocompatibility antigen, DM alpha chain isoform X1 [KO:K06752]
102973944  HLA class II histocompatibility antigen, DR alpha chain [KO:K06752]
102976012  HLA class II histocompatibility antigen, DQ beta 1 chain isoform X2 [KO:K06752]
102973764  DLA class II histocompatibility antigen, DR-1 beta chain-like isoform X1 [KO:K06752]
102976287  HLA class II histocompatibility antigen, DQ alpha 2 chain isoform X2 [KO:K06752]
102992942  HLA class II histocompatibility antigen, DO alpha chain [KO:K06752]
102974479  HLA class II histocompatibility antigen, DO beta chain [KO:K06752]
102994605  HLA class II histocompatibility antigen, DM beta chain [KO:K06752]
102978546  DLA class II histocompatibility antigen, DR-1 beta chain [KO:K06752]
102992010  LCK; LOW QUALITY PROTEIN: tyrosine-protein kinase Lck [KO:K05856] [EC:2.7.10.2]
102979279  T-cell surface glycoprotein CD3 epsilon chain [KO:K06451]
102980039  T-cell surface glycoprotein CD3 gamma chain [KO:K06452]
102989597  CD247; T-cell surface glycoprotein CD3 zeta chain [KO:K06453]
102979567  T-cell surface glycoprotein CD3 delta chain isoform X1 [KO:K06450]
102996375  tyrosine-protein kinase ZAP-70 isoform X1 [KO:K07360] [EC:2.7.10.2]
102977886  LAT; linker for activation of T-cells family member 1 isoform X1 [KO:K07362]
102992700  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
102994784  PPP3CA; protein phosphatase 3 catalytic subunit alpha isoform X1 [KO:K04348] [EC:3.1.3.16]
102973173  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X2 [KO:K04348] [EC:3.1.3.16]
102990815  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X8 [KO:K04348] [EC:3.1.3.16]
112065477  PPP3R2; LOW QUALITY PROTEIN: calcineurin subunit B type 2 [KO:K06268]
112067521  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
114484431  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
102988344  nuclear factor of activated T-cells, cytoplasmic 1 [KO:K04446]
102993777  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X5 [KO:K17332]
102984161  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
102982768  PRKCQ; protein kinase C theta type isoform X3 [KO:K18052] [EC:2.7.11.13]
102977668  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X2 [KO:K04467] [EC:2.7.11.10]
102976706  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
114485485  NF-kappa-B essential modulator-like isoform X1 [KO:K07210]
102980964  IKBKG; NF-kappa-B essential modulator [KO:K07210]
102973672  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
102995931  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
102986822  NFKBIE; NF-kappa-B inhibitor epsilon [KO:K05872]
102984305  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102989074  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102982453  FOS; protein c-Fos [KO:K04379]
102977531  MAPK12; mitogen-activated protein kinase 12 isoform X3 [KO:K04441] [EC:2.7.11.24]
102989111  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
102990302  MAPK13; mitogen-activated protein kinase 13 isoform X3 [KO:K04441] [EC:2.7.11.24]
102977994  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
102996353  MAPK8; mitogen-activated protein kinase 8 isoform X3 [KO:K04440] [EC:2.7.11.24]
102977417  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
102984741  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
102975458  JUN; transcription factor Jun [KO:K04448]
102990654  IL2; interleukin-2 [KO:K05429]
102974550  IL2RA; interleukin-2 receptor subunit alpha [KO:K05068]
102995923  IL2RB; interleukin-2 receptor subunit beta [KO:K05069]
102979617  IL2RG; cytokine receptor common subunit gamma isoform X1 [KO:K05070]
102990026  JAK3; tyrosine-protein kinase JAK3 [KO:K11218] [EC:2.7.10.2]
102978994  signal transducer and activator of transcription 5A [KO:K11223]
102994339  STAT5B; signal transducer and activator of transcription 5B [KO:K11224]
102983897  IL4; interleukin-4 [KO:K05430]
102979109  IL4R; interleukin-4 receptor subunit alpha isoform X1 [KO:K05071]
102974661  STAT6; signal transducer and activator of transcription 6 isoform X1 [KO:K11225]
102975032  GATA3; trans-acting T-cell-specific transcription factor GATA-3 isoform X1 [KO:K17895]
102983351  IL5; interleukin-5 [KO:K05428]
102989542  IL13; interleukin-13 [KO:K05435]
102984537  MAF; transcription factor Maf [KO:K09035]
102974158  JAG1; protein jagged-1 isoform X1 [KO:K06052]
102981771  JAG2; protein jagged-2 isoform X5 [KO:K21635]
102982122  NOTCH1; neurogenic locus notch homolog protein 1 [KO:K02599]
102990689  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
pcad04010  MAPK signaling pathway
pcad04020  Calcium signaling pathway
pcad04064  NF-kappa B signaling pathway
pcad04330  Notch signaling pathway
pcad04514  Cell adhesion molecules
pcad04630  JAK-STAT signaling pathway
pcad04660  T cell receptor signaling pathway
KO pathway
ko04658   
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