KEGG   PATHWAY: elk04658
Entry
elk04658                    Pathway                                
Name
Th1 and Th2 cell differentiation - Enhydra lutris kenyoni (northern sea otter)
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
elk04658  Th1 and Th2 cell differentiation
elk04658

Other DBs
GO: 0045063 0045064
Organism
Enhydra lutris kenyoni (northern sea otter) [GN:elk]
Gene
111161598  delta-like protein 3 isoform X1 [KO:K06051]
111158683  delta-like protein 1 isoform X1 [KO:K06051]
111161567  delta-like protein 4 [KO:K06051]
111143932  neurogenic locus notch homolog protein 3 [KO:K20995]
111149077  mastermind-like protein 3 [KO:K06061]
111158886  mastermind-like protein 1 [KO:K06061]
111154352  mastermind-like protein 2 [KO:K06061]
111141790  recombining binding protein suppressor of hairless-like protein [KO:K06053]
111148915  recombining binding protein suppressor of hairless isoform X1 [KO:K06053]
111153611  nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
111149956  transcription factor p65 [KO:K04735]
111142126  interferon gamma [KO:K04687]
111147686  interferon gamma receptor 1 [KO:K05132]
111155682  interferon gamma receptor 2 isoform X1 [KO:K05133]
111142881  tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
111153517  tyrosine-protein kinase JAK2 [KO:K04447] [EC:2.7.10.2]
111144592  signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
111150468  interleukin-12 subunit alpha [KO:K05406]
111141150  interleukin-12 subunit beta [KO:K05425]
111144102  interleukin-12 receptor subunit beta-1 isoform X1 [KO:K05063]
111143098  interleukin-12 receptor subunit beta-2 isoform X1 [KO:K05064]
111162402  non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
111141082  signal transducer and activator of transcription 4 [KO:K11222]
111151590  T-box transcription factor TBX21 [KO:K10166]
111154611  runt-related transcription factor 3 isoform X1 [KO:K09279]
111152451  LOW QUALITY PROTEIN: RLA class II histocompatibility antigen, DP alpha-1 chain [KO:K06752]
111152452  HLA class II histocompatibility antigen, DP beta 1 chain-like [KO:K06752]
111152151  SLA class II histocompatibility antigen, DQ haplotype C beta chain-like [KO:K06752]
111152158  SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like isoform X1 [KO:K06752]
111152168  HLA class II histocompatibility antigen, DM beta chain [KO:K06752]
111152169  HLA class II histocompatibility antigen, DM alpha chain [KO:K06752]
111152175  SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like isoform X1 [KO:K06752]
111152178  LOW QUALITY PROTEIN: DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
111152191  HLA class II histocompatibility antigen, DO beta chain isoform X1 [KO:K06752]
111152200  HLA class II histocompatibility antigen, DR alpha chain [KO:K06752]
111152259  DLA class II histocompatibility antigen, DR-1 beta chain isoform X1 [KO:K06752]
111152356  HLA class II histocompatibility antigen, DQ beta 1 chain isoform X1 [KO:K06752]
111152358  LOW QUALITY PROTEIN: HLA class II histocompatibility antigen, DR alpha chain-like [KO:K06752]
111152383  HLA class II histocompatibility antigen, DO alpha chain [KO:K06752]
111159821  T-cell surface glycoprotein CD4 isoform X1 [KO:K06454]
111142990  tyrosine-protein kinase Lck [KO:K05856] [EC:2.7.10.2]
111153962  T-cell surface glycoprotein CD3 epsilon chain isoform X1 [KO:K06451]
111153842  T-cell surface glycoprotein CD3 gamma chain [KO:K06452]
111150748  T-cell surface glycoprotein CD3 zeta chain isoform X1 [KO:K06453]
111153823  T-cell surface glycoprotein CD3 delta chain isoform X1 [KO:K06450]
111155922  tyrosine-protein kinase ZAP-70 [KO:K07360] [EC:2.7.10.2]
111162219  linker for activation of T-cells family member 1 isoform X1 [KO:K07362]
111141423  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
111144797  serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
111154144  serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
111154566  serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
111148007  calcineurin subunit B type 1 [KO:K06268]
111146053  calcineurin subunit B type 2 [KO:K06268]
111154209  nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
111141582  LOW QUALITY PROTEIN: nuclear factor of activated T-cells, cytoplasmic 2 [KO:K17332]
111152752  nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
111158618  protein kinase C theta type [KO:K18052] [EC:2.7.11.13]
111144921  inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
111144397  inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
111139191  NF-kappa-B essential modulator [KO:K07210]
111140276  NF-kappa-B inhibitor alpha isoform X1 [KO:K04734]
111161594  NF-kappa-B inhibitor beta [KO:K02581]
111147725  NF-kappa-B inhibitor epsilon [KO:K05872]
111162236  LOW QUALITY PROTEIN: mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
111142759  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
111148602  proto-oncogene c-Fos [KO:K04379]
111152267  mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
111157625  mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
111157628  mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
111152183  mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
111144860  mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
111158897  mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
111154016  mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
111143174  transcription factor AP-1 [KO:K04448]
111154869  interleukin-2 [KO:K05429]
111158621  interleukin-2 receptor subunit alpha isoform X1 [KO:K05068]
111157559  interleukin-2 receptor subunit beta isoform X1 [KO:K05069]
111161041  cytokine receptor common subunit gamma [KO:K05070]
111143876  tyrosine-protein kinase JAK3 isoform X1 [KO:K11218] [EC:2.7.10.2]
111151211  signal transducer and activator of transcription 5A [KO:K11223]
111151253  signal transducer and activator of transcription 5B [KO:K11224]
111141099  interleukin-4 [KO:K05430]
111162191  interleukin-4 receptor subunit alpha isoform X1 [KO:K05071]
111160115  signal transducer and activator of transcription 6 [KO:K11225]
111158640  trans-acting T-cell-specific transcription factor GATA-3 isoform X1 [KO:K17895]
111141209  interleukin-5 [KO:K05428]
111141294  interleukin-13 [KO:K05435]
111153073  transcription factor Maf [KO:K09035]
111141735  LOW QUALITY PROTEIN: protein jagged-1 [KO:K06052]
111148619  protein jagged-2 [KO:K21635]
111145671  neurogenic locus notch homolog protein 1 [KO:K02599]
111142867  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
elk04010  MAPK signaling pathway
elk04020  Calcium signaling pathway
elk04064  NF-kappa B signaling pathway
elk04330  Notch signaling pathway
elk04514  Cell adhesion molecules
elk04630  JAK-STAT signaling pathway
elk04660  T cell receptor signaling pathway
KO pathway
ko04658   
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