KEGG   PATHWAY: bta04658
Entry
bta04658                    Pathway                                
Name
Th1 and Th2 cell differentiation - Bos taurus (cow)
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
bta04658  Th1 and Th2 cell differentiation
bta04658

Other DBs
GO: 0045063 0045064
Organism
Bos taurus (cow) [GN:bta]
Gene
100300510  [KO:K10785]
100300850  [KO:K10784]
100336926  MAML1; mastermind-like protein 1 [KO:K06061]
100848815  [KO:K06752]
104968644  IL2RB; interleukin-2 receptor subunit beta [KO:K05069]
280795  FOS; protein c-Fos [KO:K04379]
280822  IL2; interleukin-2 precursor [KO:K05429]
280824  IL4; interleukin-4 precursor [KO:K05430]
280825  IL5; interleukin-5 precursor [KO:K05428]
280831  JUN; transcription factor Jun [KO:K04448]
281053  CD3D; T-cell surface glycoprotein CD3 delta chain precursor [KO:K06450]
281054  CD3E; T-cell surface glycoprotein CD3 epsilon chain precursor [KO:K06451]
281055  CD3G; T-cell surface glycoprotein CD3 gamma chain precursor [KO:K06452]
281056  CD247; T-cell surface glycoprotein CD3 zeta chain precursor [KO:K06453]
281073  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
281237  IFNG; interferon gamma precursor [KO:K04687]
281247  IL13; interleukin-13 precursor [KO:K05435]
281854  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
281855  IKBKG; NF-kappa-B essential modulator [KO:K07210]
281856  IL12A; interleukin-12 subunit alpha precursor [KO:K05406]
281857  IL12B; interleukin-12 subunit beta precursor [KO:K05425]
281861  IL2RA; interleukin-2 receptor subunit alpha precursor [KO:K05068]
281862  IL2RG; cytokine receptor common subunit gamma precursor [KO:K05070]
281987  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 [KO:K01116] [EC:3.1.4.11]
282291  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
282321  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
282375  STAT5A; signal transducer and activator of transcription 5A [KO:K11223]
282376  STAT5B; signal transducer and activator of transcription 5B [KO:K11224]
282452  IL12RB2; interleukin-12 receptor subunit beta-2 precursor [KO:K05064]
282490  BOLA-DMA; HLA class II histocompatibility antigen, DM alpha chain precursor [KO:K06752]
282491  BOLA-DMB; major histocompatibility complex, class II, DM beta precursor [KO:K06752]
282493  BOLA-DOB; HLA class II histocompatibility antigen, DO beta chain precursor [KO:K06752]
282494  BOLA-DQA5; major histocompatibility complex, class II, DQ alpha 5 precursor [KO:K06752]
282495  BOLA-DQB; major histocompatibility complex, class II, DQ beta precursor [KO:K06752]
282497  BOLA-DYA; major histocompatibility complex, class II, DY alpha precursor [KO:K06752]
282498  BOLA-DYB; major histocompatibility complex, class II, DY beta precursor [KO:K06752]
282530  BOLA-DRB3; major histocompatibility complex, class II, DRB3 [KO:K06752]
282535  BOLA-DQA2; major histocompatibility complex, class II, DQ alpha 2 [KO:K06752]
286852  PPP3CA; protein phosphatase 3 catalytic subunit alpha [KO:K04348] [EC:3.1.3.16]
327672  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
353105  STAT6; signal transducer and activator of transcription 6 [KO:K11225]
404154  IL4R; interleukin-4 receptor subunit alpha precursor [KO:K05071]
407098  CD4; T-cell surface glycoprotein CD4 precursor [KO:K06454]
504509  ZAP70; tyrosine-protein kinase ZAP-70 [KO:K07360] [EC:2.7.10.2]
505169  GATA3; trans-acting T-cell-specific transcription factor GATA-3 [KO:K17895]
505901  PRKCQ; protein kinase C theta type [KO:K18052] [EC:2.7.11.13]
505993  DLL3; delta-like protein 3 precursor [KO:K06051]
506214  BOLA-DRA; major histocompatibility complex, class II, DR alpha precursor [KO:K06752]
506727  NFKBIE; NF-kappa-B inhibitor epsilon [KO:K05872]
508233  RELA; transcription factor p65 [KO:K04735]
508619  IFNGR1; interferon gamma receptor 1 precursor [KO:K05132]
508890  LCK; tyrosine-protein kinase Lck [KO:K05856] [EC:2.7.10.2]
509513  [KO:K10785]
510185  [KO:K05069]
510814  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
511224  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 [KO:K04446]
512484  TYK2; non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
512943  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
513730  NOTCH2; neurogenic locus notch homolog protein 2 isoform X1 [KO:K20994]
514735  LAT; linker for activation of T-cells family member 1 precursor [KO:K07362]
514889  IFNGR2; interferon gamma receptor 2 isoform X1 [KO:K05133]
515988  STAT4; signal transducer and activator of transcription 4 [KO:K11222]
517405  JAG2; protein jagged-2 isoform X1 [KO:K21635]
518746  DLL4; delta-like protein 4 precursor [KO:K06051]
521194  MAML2; mastermind-like protein 2 [KO:K06061]
524299  IL12RB1; interleukin-12 receptor subunit beta-1 [KO:K05063]
525246  JAK2; tyrosine-protein kinase JAK2 isoform X1 [KO:K04447] [EC:2.7.10.2]
525408  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
525727  BOLA-DOA; HLA class II histocompatibility antigen, DO alpha chain precursor [KO:K06752]
530401  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
531391  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
533527  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform [KO:K04348] [EC:3.1.3.16]
534125  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
534492  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
535327  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
537201  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
537631  MAPK10; mitogen-activated protein kinase 10 isoform 2 [KO:K04440] [EC:2.7.11.24]
538276  JAK3; tyrosine-protein kinase JAK3 [KO:K11218] [EC:2.7.10.2]
538700  BOLA-DRB2; HLA class II histocompatibility antigen, DR beta 5 chain isoform X3 [KO:K06752]
538933  TBX21; T-box transcription factor TBX21 [KO:K10166]
539241  BLA-DQB; boLa class II histocompatibility antigen, DQB*0101 beta chain precursor [KO:K06752]
539941  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
540059  RBPJL; recombining binding protein suppressor of hairless-like protein [KO:K06053]
540588  MAML3; mastermind-like protein 3 isoform X1 [KO:K06061]
541127  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 [KO:K17333]
616115  NFKB1; nuclear factor NF-kappa-B p105 subunit [KO:K02580]
617389  RUNX3; runt-related transcription factor 3 isoform 2 [KO:K09279]
617585  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
618722  DSB; MHC class II antigen DS beta [KO:K06752]
618906  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
767866  NOTCH1; neurogenic locus notch homolog protein 1 isoform X1 [KO:K02599]
767928  RBPJ; recombining binding protein suppressor of hairless [KO:K06053]
782481  MAF; transcription factor Maf [KO:K09035]
783681  JAG1; protein jagged-1 precursor [KO:K06052]
788775  DLL1; delta-like protein 1 [KO:K06051]
789485  NOTCH3; neurogenic locus notch homolog protein 3 [KO:K20995]
790867  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform [KO:K04348] [EC:3.1.3.16]
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
bta04010  MAPK signaling pathway
bta04020  Calcium signaling pathway
bta04064  NF-kappa B signaling pathway
bta04330  Notch signaling pathway
bta04514  Cell adhesion molecule (CAM) interaction
bta04630  JAK-STAT signaling pathway
bta04660  T cell receptor signaling pathway
KO pathway
ko04658   

DBGET integrated database retrieval system