KEGG   PATHWAY: dle04658
Entry
dle04658                    Pathway                                
Name
Th1 and Th2 cell differentiation - Delphinapterus leucas (beluga 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
dle04658  Th1 and Th2 cell differentiation
dle04658

Other DBs
GO: 0045063 0045064
Organism
Delphinapterus leucas (beluga whale) [GN:dle]
Gene
111163022  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
111163267  RUNX3; runt-related transcription factor 3 [KO:K09279]
111163885  IFNGR2; interferon gamma receptor 2 [KO:K05133]
111165629  JAG1; protein jagged-1 [KO:K06052]
111166017  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
111166198  IFNGR1; interferon gamma receptor 1 [KO:K05132]
111166337  [KO:K11223]
111166371  TBX21; T-box transcription factor TBX21 [KO:K10166]
111166483  [KO:K11224]
111166554  NOTCH3; neurogenic locus notch homolog protein 3 isoform X1 [KO:K20995]
111166590  JAK3; tyrosine-protein kinase JAK3 [KO:K11218] [EC:2.7.10.2]
111166653  IL12RB1; interleukin-12 receptor subunit beta-1 isoform X1 [KO:K05063]
111166898  CD3E; T-cell surface glycoprotein CD3 epsilon chain [KO:K06451]
111166923  CD3D; T-cell surface glycoprotein CD3 delta chain [KO:K06450]
111166936  CD3G; T-cell surface glycoprotein CD3 gamma chain [KO:K06452]
111167284  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
111167315  CD247; T-cell surface glycoprotein CD3 zeta chain isoform X1 [KO:K06453]
111167807  IL2RG; cytokine receptor common subunit gamma isoform X1 [KO:K05070]
111167988  DLL1; delta-like protein 1 isoform X1 [KO:K06051]
111168108  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
111168397  MAML2; mastermind-like protein 2 [KO:K06061]
111169035  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
111169262  MAML1; mastermind-like protein 1 [KO:K06061]
111169265  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
111169895  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
111170635  IL12B; interleukin-12 subunit beta [KO:K05425]
111170864  [KO:K06053]
111170969  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
111171298  [KO:K10784]
111171663  STAT1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
111171668  STAT4; signal transducer and activator of transcription 4 isoform X1 [KO:K11222]
111172396  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
111173225  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
111173552  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
111173770  IFNG; interferon gamma [KO:K04687]
111173850  STAT6; signal transducer and activator of transcription 6 isoform X4 [KO:K11225]
111174517  IL12A; interleukin-12 subunit alpha [KO:K05406]
111174651  JAK2; tyrosine-protein kinase JAK2 [KO:K04447] [EC:2.7.10.2]
111175513  LCK; tyrosine-protein kinase Lck [KO:K05856] [EC:2.7.10.2]
111175871  JUN; transcription factor AP-1 [KO:K04448]
111175998  JAG2; protein jagged-2 isoform X1 [KO:K21635]
111176238  FOS; proto-oncogene c-Fos [KO:K04379]
111176687  CD4; T-cell surface glycoprotein CD4 [KO:K06454]
111177023  NOTCH1; neurogenic locus notch homolog protein 1 [KO:K02599]
111177977  IL2RA; interleukin-2 receptor subunit alpha [KO:K05068]
111177982  PRKCQ; protein kinase C theta type isoform X1 [KO:K18052] [EC:2.7.11.13]
111177990  GATA3; trans-acting T-cell-specific transcription factor GATA-3 isoform X1 [KO:K17895]
111178439  IL12RB2; interleukin-12 receptor subunit beta-2 isoform X1 [KO:K05064]
111178461  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
111178664  [KO:K06752]
111178666  [KO:K06752]
111178668  [KO:K06752]
111178736  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
111178738  MAPK13; mitogen-activated protein kinase 13 isoform X2 [KO:K04441] [EC:2.7.11.24]
111178873  NFKBIE; NF-kappa-B inhibitor epsilon isoform X1 [KO:K05872]
111178925  [KO:K06752]
111178927  [KO:K06752]
111178928  [KO:K06752]
111178929  [KO:K06752]
111178931  [KO:K06752]
111179107  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
111179110  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
111179119  MAML3; mastermind-like protein 3 isoform X1 [KO:K06061]
111179475  MAF; LOW QUALITY PROTEIN: transcription factor Maf [KO:K09035]
111179609  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
111179961  NOTCH2; neurogenic locus notch homolog protein 2 isoform X1 [KO:K20994]
111180865  DLL3; delta-like protein 3 [KO:K06051]
111180882  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
111181726  DLL4; delta-like protein 4 [KO:K06051]
111182181  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
111182203  LAT; linker for activation of T-cells family member 1 isoform X1 [KO:K07362]
111182213  IL4R; interleukin-4 receptor subunit alpha isoform X1 [KO:K05071]
111182417  IL5; interleukin-5 [KO:K05428]
111182418  IL4; interleukin-4 [KO:K05430]
111182419  IL13; interleukin-13 [KO:K05435]
111183521  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
111183745  RELA; transcription factor p65 isoform X1 [KO:K04735]
111184170  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
111184415  RBPJL; recombining binding protein suppressor of hairless-like protein [KO:K06053]
111186150  IL2; interleukin-2 [KO:K05429]
111186349  IL2RB; interleukin-2 receptor subunit beta isoform X1 [KO:K05069]
111186361  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
111186364  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
111186607  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
111186778  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
111187417  [KO:K07360] [EC:2.7.10.2]
111188120  PPP3R2; LOW QUALITY PROTEIN: calcineurin subunit B type 2 [KO:K06268]
115801463  [KO:K06752]
115804208  [KO:K06752]
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
dle04010  MAPK signaling pathway
dle04020  Calcium signaling pathway
dle04064  NF-kappa B signaling pathway
dle04330  Notch signaling pathway
dle04514  Cell adhesion molecules
dle04630  JAK-STAT signaling pathway
dle04660  T cell receptor signaling pathway
KO pathway
ko04658   

DBGET integrated database retrieval system