KEGG   PATHWAY: ray04658
Entry
ray04658                    Pathway                                
Name
Th1 and Th2 cell differentiation - Rousettus aegyptiacus (Egyptian rousette)
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
ray04658  Th1 and Th2 cell differentiation
ray04658

Other DBs
GO: 0045063 0045064
Organism
Rousettus aegyptiacus (Egyptian rousette) [GN:ray]
Gene
107521802  DLL3; delta-like protein 3 [KO:K06051]
107500164  DLL1; delta-like protein 1 isoform X1 [KO:K06051]
107514489  DLL4; delta-like protein 4 [KO:K06051]
107517220  NOTCH3; neurogenic locus notch homolog protein 3 isoform X1 [KO:K20995]
107518359  MAML2; mastermind-like protein 2 [KO:K06061]
107515337  MAML3; mastermind-like protein 3 [KO:K06061]
107512318  MAML1; mastermind-like protein 1 [KO:K06061]
107514592  RBPJL; recombining binding protein suppressor of hairless-like protein [KO:K06053]
107505448  RBPJ; LOW QUALITY PROTEIN: recombining binding protein suppressor of hairless [KO:K06053]
107517900  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
107497522  RELA; transcription factor p65 [KO:K04735]
107512682  IFNG; interferon gamma [KO:K04687]
107521298  IFNGR1; interferon gamma receptor 1 isoform X1 [KO:K05132]
107519538  IFNGR2; interferon gamma receptor 2 [KO:K05133]
107517940  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
107507294  JAK2; tyrosine-protein kinase JAK2 [KO:K04447] [EC:2.7.10.2]
107519182  STAT1; LOW QUALITY PROTEIN: signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
107512954  IL12A; interleukin-12 subunit alpha [KO:K05406]
107521891  IL12B; interleukin-12 subunit beta [KO:K05425]
107521689  IL12RB1; interleukin-12 receptor subunit beta-1 isoform X1 [KO:K05063]
107520563  IL12RB2; LOW QUALITY PROTEIN: interleukin-12 receptor subunit beta-2 [KO:K05064]
107515075  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
107519219  STAT4; signal transducer and activator of transcription 4 isoform X1 [KO:K11222]
107520715  TBX21; LOW QUALITY PROTEIN: T-box transcription factor TBX21 [KO:K10166]
107499934  RUNX3; runt-related transcription factor 3 isoform X1 [KO:K09279]
107506765  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
107506766  HLA class II histocompatibility antigen, DR alpha chain [KO:K06752]
107505772  HLA class II histocompatibility antigen, DQ alpha 2 chain-like [KO:K06752]
107505773  boLa class II histocompatibility antigen, DQB*0101 beta chain-like [KO:K06752]
107505774  HLA class II histocompatibility antigen, DQ alpha 2 chain-like [KO:K06752]
107511941  H-2 class II histocompatibility antigen, A-R alpha chain-like [KO:K06752]
107511990  HLA class II histocompatibility antigen, DO alpha chain [KO:K06752]
107511992  HLA class II histocompatibility antigen, DM beta chain [KO:K06752]
107511993  HLA class II histocompatibility antigen, DM alpha chain isoform X1 [KO:K06752]
107511999  HLA class II histocompatibility antigen, DO beta chain isoform X1 [KO:K06752]
107512001  HLA class II histocompatibility antigen, DQ beta 1 chain-like isoform X1 [KO:K06752]
107507331  HLA class II histocompatibility antigen, DQ alpha 2 chain-like [KO:K06752]
107507332  SLA class II histocompatibility antigen, DQ haplotype C beta chain-like isoform X1 [KO:K06752]
107513587  LCK; tyrosine-protein kinase Lck isoform X1 [KO:K05856] [EC:2.7.10.2]
107516045  CD3E; T-cell surface glycoprotein CD3 epsilon chain [KO:K06451]
107516027  CD3G; T-cell surface glycoprotein CD3 gamma chain isoform X1 [KO:K06452]
107516945  uncharacterized protein LOC107516945 [KO:K10785]
107512743  CD247; T-cell surface glycoprotein CD3 zeta chain isoform X1 [KO:K06453]
107516062  CD3D; T-cell surface glycoprotein CD3 delta chain [KO:K06450]
107509971  tyrosine-protein kinase ZAP-70 [KO:K07360] [EC:2.7.10.2]
107515810  LAT; linker for activation of T-cells family member 1 [KO:K07362]
107506741  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
107516843  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
107517885  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
107509227  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
107506933  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
107499586  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
107500851  NFATC1; LOW QUALITY PROTEIN: nuclear factor of activated T-cells, cytoplasmic 1 [KO:K04446]
107510349  nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
107498687  nuclear factor of activated T-cells, cytoplasmic 2-like isoform X1 [KO:K17332]
107520480  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
107505977  PRKCQ; protein kinase C theta type isoform X1 [KO:K18052] [EC:2.7.11.13]
107499756  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
107501353  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
107499585  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
107514416  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
107520958  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
107501997  NFKBIE; NF-kappa-B inhibitor epsilon [KO:K05872]
107515836  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
107497830  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
107498912  FOS; proto-oncogene c-Fos [KO:K04379]
107497883  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
107497895  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
107500264  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
107500274  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
107512328  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
107509910  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
107515392  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
107518352  JUN; transcription factor AP-1 [KO:K04448]
107505383  IL2; interleukin-2 isoform X1 [KO:K05429]
107505982  IL2RA; interleukin-2 receptor subunit alpha isoform X1 [KO:K05068]
107519288  IL2RB; interleukin-2 receptor subunit beta isoform X1 [KO:K05069]
107513773  IL2RG; cytokine receptor common subunit gamma isoform X1 [KO:K05070]
107521798  JAK3; tyrosine-protein kinase JAK3 [KO:K11218] [EC:2.7.10.2]
107513821  signal transducer and activator of transcription 5A [KO:K11223]
107513822  STAT5B; signal transducer and activator of transcription 5B isoform X1 [KO:K11224]
107497063  IL4; interleukin-4 [KO:K05430]
107506151  IL4R; interleukin-4 receptor subunit alpha isoform X1 [KO:K05071]
107501843  STAT6; signal transducer and activator of transcription 6 [KO:K11225]
107505969  GATA3; trans-acting T-cell-specific transcription factor GATA-3 isoform X1 [KO:K17895]
107497016  IL5; LOW QUALITY PROTEIN: interleukin-5 [KO:K05428]
107497023  IL13; interleukin-13 [KO:K05435]
107514376  MAF; LOW QUALITY PROTEIN: transcription factor Maf [KO:K09035]
107507103  JAG1; protein jagged-1 isoform X1 [KO:K06052]
107498372  JAG2; LOW QUALITY PROTEIN: protein jagged-2 [KO:K21635]
107514882  NOTCH1; neurogenic locus notch homolog protein 1 [KO:K02599]
107514333  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
ray04010  MAPK signaling pathway
ray04020  Calcium signaling pathway
ray04064  NF-kappa B signaling pathway
ray04330  Notch signaling pathway
ray04514  Cell adhesion molecules
ray04630  JAK-STAT signaling pathway
ray04660  T cell receptor signaling pathway
KO pathway
ko04658   
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