KEGG   PATHWAY: ko04658
Entry
ko04658                     Pathway                                

Name
Th1 and Th2 cell differentiation
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
ko04658  Th1 and Th2 cell differentiation
ko04658

Disease
H01413  Adams-Oliver syndrome
Other DBs
GO: 0045063 0045064
Orthology
K06051  delta
K20995  Notch 3
K06061  mastermind
K06053  recombining binding protein suppressor of hairless
K02580  nuclear factor NF-kappa-B p105 subunit
K04735  transcription factor p65
K04687  interferon gamma
K05132  interferon gamma receptor 1
K05133  interferon gamma receptor 2
K11217  Janus kinase 1 [EC:2.7.10.2]
K04447  Janus kinase 2 [EC:2.7.10.2]
K11220  signal transducer and activator of transcription 1
K05406  interleukin 12A
K05425  interleukin 12B
K05063  interleukin 12 receptor beta-1
K05064  interleukin 12 receptor beta-2
K11219  non-receptor tyrosine-protein kinase TYK2 [EC:2.7.10.2]
K11222  signal transducer and activator of transcription 4
K10166  T-box protein 21
K09279  runt-related transcription factor 3
K06752  MHC class II antigen
K06454  T-cell surface glycoprotein CD4
K05856  lymphocyte cell-specific protein tyrosine kinase [EC:2.7.10.2]
K06451  T-cell surface glycoprotein CD3 epsilon chain
K06452  T-cell surface glycoprotein CD3 gamma chain
K10784  T cell receptor alpha chain V region
K10785  T-cell receptor beta chain V region
K06453  CD3Z antigen, zeta polypeptide
K06450  T-cell surface glycoprotein CD3 delta chain
K07360  tyrosine-protein kinase ZAP-70 [EC:2.7.10.2]
K07362  linker for activation of T cells
K01116  phosphatidylinositol phospholipase C, gamma-1 [EC:3.1.4.11]
K04348  serine/threonine-protein phosphatase 2B catalytic subunit [EC:3.1.3.16]
K06268  serine/threonine-protein phosphatase 2B regulatory subunit
K04446  nuclear factor of activated T-cells, cytoplasmic 1
K17332  nuclear factor of activated T-cells, cytoplasmic 2
K17333  nuclear factor of activated T-cells, cytoplasmic 3
K18052  novel protein kinase C theta type [EC:2.7.11.13]
K04467  inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:2.7.11.10]
K07209  inhibitor of nuclear factor kappa-B kinase subunit beta [EC:2.7.11.10]
K07210  inhibitor of nuclear factor kappa-B kinase subunit gamma
K04734  NF-kappa-B inhibitor alpha
K02581  NF-kappa-B inhibitor beta
K05872  NF-kappa-B inhibitor epsilon
K04371  mitogen-activated protein kinase 1/3 [EC:2.7.11.24]
K04379  proto-oncogene protein c-fos
K04441  p38 MAP kinase [EC:2.7.11.24]
K04440  mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24]
K04448  transcription factor AP-1
K05429  interleukin 2
K05068  interleukin 2 receptor alpha
K05069  interleukin 2 receptor beta
K05070  interleukin 2 receptor gamma
K11218  Janus kinase 3 [EC:2.7.10.2]
K11223  signal transducer and activator of transcription 5A
K11224  signal transducer and activator of transcription 5B
K05430  interleukin 4
K05071  interleukin 4 receptor
K11225  signal transducer and activator of transcription 6
K17895  GATA-binding protein 3
K05428  interleukin 5
K05435  interleukin 13
K09035  transcription factor Maf
K06052  jagged-1
K21635  jagged-2
K02599  Notch 1
K20994  Notch 2
Compound
C00076  Calcium cation
C00165  Diacylglycerol
C01245  D-myo-Inositol 1,4,5-trisphosphate
Reference
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  Authors
Pahan K, Mondal S
  Title
Crosstalk between Nitric Oxide and T helper cells.
  Journal
J Clin Cell Immunol 3:e109 (2012)
Reference
  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
ko04010  MAPK signaling pathway
ko04020  Calcium signaling pathway
ko04064  NF-kappa B signaling pathway
ko04330  Notch signaling pathway
ko04514  Cell adhesion molecules
ko04630  JAK-STAT signaling pathway
ko04660  T cell receptor signaling pathway
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