KEGG   PATHWAY: tmu04658
Entry
tmu04658                    Pathway                                
Name
Th1 and Th2 cell differentiation - Trichechus manatus latirostris (Florida manatee)
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
tmu04658  Th1 and Th2 cell differentiation
tmu04658

Other DBs
GO: 0045063 0045064
Organism
Trichechus manatus latirostris (Florida manatee) [GN:tmu]
Gene
101360018  delta-like protein 1 [KO:K06051]
101351506  delta-like protein 4 [KO:K06051]
101361650  delta-like protein 3 [KO:K06051]
101358955  neurogenic locus notch homolog protein 3 [KO:K20995]
101341429  mastermind-like protein 2 [KO:K06061]
111822201  mastermind-like protein 3 [KO:K06061]
101350345  mastermind-like protein 1 [KO:K06061]
101350933  recombining binding protein suppressor of hairless-like protein [KO:K06053]
101359358  recombining binding protein suppressor of hairless isoform X1 [KO:K06053]
101351866  nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
101361706  transcription factor p65 [KO:K04735]
101346429  interferon gamma [KO:K04687]
101345582  interferon gamma receptor 1 isoform X1 [KO:K05132]
101361970  interferon gamma receptor 2 [KO:K05133]
101346613  tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
101354918  tyrosine-protein kinase JAK2 [KO:K04447] [EC:2.7.10.2]
101357916  signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
101353752  interleukin-12 subunit alpha [KO:K05406]
101344352  interleukin-12 subunit beta [KO:K05425]
101351266  interleukin-12 receptor subunit beta-1 [KO:K05063]
101352491  interleukin-12 receptor subunit beta-2 [KO:K05064]
101357635  non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
101351364  signal transducer and activator of transcription 4 isoform X1 [KO:K11222]
101346659  T-box transcription factor TBX21 [KO:K10166]
101343312  HLA class II histocompatibility antigen, DM alpha chain isoform X1 [KO:K06752]
101343065  HLA class II histocompatibility antigen, DO alpha chain [KO:K06752]
101344101  LOW QUALITY PROTEIN: boLa class II histocompatibility antigen, DQB*0101 beta chain-like [KO:K06752]
101345015  boLa class II histocompatibility antigen, DQB*0101 beta chain-like [KO:K06752]
101361245  LOW QUALITY PROTEIN: DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
101342567  HLA class II histocompatibility antigen, DP beta 1 chain [KO:K06752]
101342817  HLA class II histocompatibility antigen, DP alpha 1 chain isoform X2 [KO:K06752]
101342571  HLA class II histocompatibility antigen, DP beta 1 chain-like [KO:K06752]
101343573  HLA class II histocompatibility antigen, DM beta chain [KO:K06752]
101345267  HLA class II histocompatibility antigen, DQ alpha 2 chain-like [KO:K06752]
101345522  HLA class II histocompatibility antigen, DR alpha chain [KO:K06752]
101348755  HLA class II histocompatibility antigen, DP alpha 1 chain-like [KO:K06752]
101343648  T-cell surface glycoprotein CD4 isoform X3 [KO:K06454]
101358037  tyrosine-protein kinase Lck isoform X2 [KO:K05856] [EC:2.7.10.2]
101359660  T-cell surface glycoprotein CD3 epsilon chain isoform X1 [KO:K06451]
101352744  T-cell surface glycoprotein CD3 gamma chain isoform X1 [KO:K06452]
111819117  uncharacterized protein LOC111819117 [KO:K10784]
101361451  LOW QUALITY PROTEIN: uncharacterized protein LOC101361451 [KO:K10785]
105756611  uncharacterized protein LOC105756611 [KO:K10785]
101342429  uncharacterized protein LOC101342429 [KO:K10785]
101345999  T-cell surface glycoprotein CD3 zeta chain isoform X1 [KO:K06453]
101353008  T-cell surface glycoprotein CD3 delta chain isoform X1 [KO:K06450]
101347632  tyrosine-protein kinase ZAP-70 [KO:K07360] [EC:2.7.10.2]
101356413  linker for activation of T-cells family member 1 isoform X2 [KO:K07362]
101359597  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X2 [KO:K01116] [EC:3.1.4.11]
101353424  serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X2 [KO:K04348] [EC:3.1.3.16]
101357894  serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
101347440  serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform [KO:K04348] [EC:3.1.3.16]
101343394  calcineurin subunit B type 1 isoform X2 [KO:K06268]
101355330  calcineurin subunit B type 2 [KO:K06268]
101359059  nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
101355751  nuclear factor of activated T-cells, cytoplasmic 2 isoform X2 [KO:K17332]
101352434  nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
101355872  protein kinase C theta type isoform X2 [KO:K18052] [EC:2.7.11.13]
101341290  inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
101351256  inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
101347574  NF-kappa-B essential modulator isoform X1 [KO:K07210]
101355353  NF-kappa-B inhibitor alpha [KO:K04734]
101357924  NF-kappa-B inhibitor beta [KO:K02581]
101344638  NF-kappa-B inhibitor epsilon [KO:K05872]
101340589  mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
101358526  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101357016  proto-oncogene c-Fos [KO:K04379]
101352466  mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
101347350  mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
101361614  mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
101361872  mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
101351734  mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
101351967  mitogen-activated protein kinase 9 isoform X2 [KO:K04440] [EC:2.7.11.24]
101343546  mitogen-activated protein kinase 8 isoform X4 [KO:K04440] [EC:2.7.11.24]
101361653  transcription factor AP-1 [KO:K04448]
101360180  interleukin-2 [KO:K05429]
101342095  interleukin-2 receptor subunit alpha [KO:K05068]
101344371  interleukin-2 receptor subunit beta [KO:K05069]
101359472  cytokine receptor common subunit gamma isoform X1 [KO:K05070]
101345231  tyrosine-protein kinase JAK3 [KO:K11218] [EC:2.7.10.2]
101343407  signal transducer and activator of transcription 5A isoform X1 [KO:K11223]
101354148  signal transducer and activator of transcription 5B [KO:K11224]
101341010  interleukin-4 [KO:K05430]
101351007  interleukin-4 receptor subunit alpha [KO:K05071]
101343014  signal transducer and activator of transcription 6 [KO:K11225]
101354015  trans-acting T-cell-specific transcription factor GATA-3 isoform X2 [KO:K17895]
101341771  interleukin-5 isoform X2 [KO:K05428]
101341264  interleukin-13 [KO:K05435]
101354200  protein jagged-1 [KO:K06052]
101361011  protein jagged-2 [KO:K21635]
101348816  neurogenic locus notch homolog protein 1 [KO:K02599]
101356889  neurogenic locus notch homolog protein 2 isoform X2 [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
tmu04010  MAPK signaling pathway
tmu04020  Calcium signaling pathway
tmu04064  NF-kappa B signaling pathway
tmu04330  Notch signaling pathway
tmu04514  Cell adhesion molecules
tmu04630  JAK-STAT signaling pathway
tmu04660  T cell receptor signaling pathway
KO pathway
ko04658   
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