KEGG   PATHWAY: cfa04658
Entry
cfa04658                    Pathway                                
Name
Th1 and Th2 cell differentiation - Canis lupus familiaris (dog)
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
cfa04658  Th1 and Th2 cell differentiation
cfa04658

Other DBs
GO: 0045063 0045064
Organism
Canis lupus familiaris (dog) [GN:cfa]
Gene
484508  DLL3; delta-like protein 3 [KO:K06051]
607575  DLL4; delta-like protein 4 isoform X2 [KO:K06051]
100688936  DLL1; delta-like protein 1 [KO:K06051]
610439  NOTCH3; neurogenic locus notch homolog protein 3 [KO:K20995]
485116  MAML2; mastermind-like protein 2 isoform X2 [KO:K06061]
481457  MAML1; mastermind-like protein 1 isoform X5 [KO:K06061]
119863905  mastermind-like protein 3 [KO:K06061]
485892  RBPJL; recombining binding protein suppressor of hairless-like protein isoform X5 [KO:K06053]
479122  RBPJ; recombining binding protein suppressor of hairless isoform X2 [KO:K06053]
442859  NFKB1; nuclear factor NF-kappa-B p105 subunit [KO:K02580]
483729  RELA; transcription factor p65 isoform X2 [KO:K04735]
403801  IFNG; interferon gamma precursor [KO:K04687]
100856077  IFNGR1; interferon gamma receptor 1 [KO:K05132]
487739  IFNGR2; interferon gamma receptor 2 isoform X3 [KO:K05133]
442952  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
484185  JAK2; tyrosine-protein kinase JAK2 isoform X13 [KO:K04447] [EC:2.7.10.2]
488449  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
403977  IL12A; interleukin-12 subunit alpha precursor [KO:K05406]
403976  IL12B; interleukin-12 subunit beta precursor [KO:K05425]
484828  IL12RB1; interleukin-12 receptor subunit beta-1 isoform X1 [KO:K05063]
489550  IL12RB2; interleukin-12 receptor subunit beta-2 precursor [KO:K05064]
476714  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
478845  STAT4; signal transducer and activator of transcription 4 isoform X1 [KO:K11222]
491044  TBX21; T-box transcription factor TBX21 [KO:K10166]
119870408  RUNX3; runt-related transcription factor 3 [KO:K09279]
474860  HLA-DRB1; DLA class II histocompatibility antigen, DR-1 beta chain precursor [KO:K06752]
481731  DLA-DRA; MHC class II DR alpha chain precursor [KO:K06752]
607786  DLA-DOB; major histocompatibility complex, class II, DO beta precursor [KO:K06752]
607827  DLA-DMB; major histocompatibility complex, class II, DM beta precursor [KO:K06752]
481732  DLA-DMA; major histocompatibility complex, class II, DM alpha precursor [KO:K06752]
474869  DLA-DOA; HLA class II histocompatibility antigen, DO alpha chain-like precursor [KO:K06752]
100856137  HLA class II histocompatibility antigen, DQ beta 2 chain isoform X1 [KO:K06752]
403931  CD4; T-cell surface glycoprotein CD4 precursor [KO:K06454]
478151  LCK; tyrosine-protein kinase Lck [KO:K05856] [EC:2.7.10.2]
442981  CD3E; T-cell surface glycoprotein CD3 epsilon chain isoform X1 [KO:K06451]
489383  CD3G; T-cell surface glycoprotein CD3 gamma chain [KO:K06452]
611571  CD247; T-cell surface glycoprotein CD3 zeta chain isoform X1 [KO:K06453]
479419  CD3D; T-cell surface glycoprotein CD3 delta chain [KO:K06450]
100271860  ZAP70; tyrosine-protein kinase ZAP-70 [KO:K07360] [EC:2.7.10.2]
607947  LAT; linker for activation of T-cells family member 1 isoform X1 [KO:K07362]
485874  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
609027  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X3 [KO:K04348] [EC:3.1.3.16]
403486  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform [KO:K04348] [EC:3.1.3.16]
479248  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
612559  PPP3R1; calcineurin subunit B type 1 isoform X2 [KO:K06268]
610453  PPP3R2; calcineurin subunit B type 2 isoform X5 [KO:K06268]
483925  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X3 [KO:K04446]
485930  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
479678  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
478013  PRKCQ; protein kinase C theta type isoform X1 [KO:K18052] [EC:2.7.11.13]
477796  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X3 [KO:K04467] [EC:2.7.11.10]
482839  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
480291  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
484519  NFKBIB; NF-kappa-B inhibitor beta isoform X2 [KO:K02581]
102155642  NFKBIE; NF-kappa-B inhibitor epsilon [KO:K05872]
477575  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
100855877  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
490792  FOS; proto-oncogene c-Fos [KO:K04379]
403856  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
607019  MAPK11; mitogen-activated protein kinase 11 isoform X2 [KO:K04441] [EC:2.7.11.24]
607023  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
612821  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
477746  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
478464  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
474652  MAPK9; mitogen-activated protein kinase 9 isoform X4 [KO:K04440] [EC:2.7.11.24]
609429  JUN; transcription factor AP-1 [KO:K04448]
403989  IL2; interleukin-2 precursor [KO:K05429]
403870  IL2RA; interleukin-2 receptor subunit alpha precursor [KO:K05068]
403439  IL2RB; interleukin-2 receptor subunit beta isoform 2 precursor [KO:K05069]
403851  IL2RG; cytokine receptor common subunit gamma precursor [KO:K05070]
610004  JAK3; tyrosine-protein kinase JAK3 isoform X1 [KO:K11218] [EC:2.7.10.2]
490968  STAT5A; signal transducer and activator of transcription 5A isoform X2 [KO:K11223]
490969  STAT5B; signal transducer and activator of transcription 5B isoform X2 [KO:K11224]
403785  IL4; interleukin-4 precursor [KO:K05430]
489957  IL4R; interleukin-4 receptor subunit alpha isoform X2 [KO:K05071]
100142679  STAT6; signal transducer and activator of transcription 6 [KO:K11225]
487134  GATA3; trans-acting T-cell-specific transcription factor GATA-3 isoform X8 [KO:K17895]
403790  IL5; interleukin-5 precursor [KO:K05428]
442990  IL13; interleukin-13 precursor [KO:K05435]
102156419  MAF; LOW QUALITY PROTEIN: transcription factor Maf [KO:K09035]
485769  JAG1; protein jagged-1 [KO:K06052]
490882  JAG2; protein jagged-2 isoform X5 [KO:K21635]
480676  NOTCH1; neurogenic locus notch homolog protein 1 [KO:K02599]
483148  NOTCH2; neurogenic locus notch homolog protein 2 isoform X1 [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
cfa04010  MAPK signaling pathway
cfa04020  Calcium signaling pathway
cfa04064  NF-kappa B signaling pathway
cfa04330  Notch signaling pathway
cfa04514  Cell adhesion molecules
cfa04630  JAK-STAT signaling pathway
cfa04660  T cell receptor signaling pathway
KO pathway
ko04658   
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