KEGG   PATHWAY: cjc04658
Entry
cjc04658                    Pathway                                
Name
Th1 and Th2 cell differentiation - Callithrix jacchus (white-tufted-ear marmoset)
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
cjc04658  Th1 and Th2 cell differentiation
cjc04658

Other DBs
GO: 0045063 0045064
Organism
Callithrix jacchus (white-tufted-ear marmoset) [GN:cjc]
Gene
100385000  CD4; T-cell surface glycoprotein CD4 precursor [KO:K06454]
100385427  CAJA-DRA; HLA class II histocompatibility antigen, DR alpha chain precursor [KO:K06752]
100385553  MAF; transcription factor Maf isoform X1 [KO:K09035]
100385835  JAK1; tyrosine-protein kinase JAK1 isoform X1 [KO:K11217] [EC:2.7.10.2]
100386155  CAJA-DRB1; HLA class II histocompatibility antigen, DRB1-13 beta chain-like precursor [KO:K06752]
100386369  PPP3CA; protein phosphatase 3 catalytic subunit alpha isoform X1 [KO:K04348] [EC:3.1.3.16]
100386452  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X5 [KO:K04348] [EC:3.1.3.16]
100386516  IFNGR1; interferon gamma receptor 1 isoform X1 [KO:K05132]
100386797  MAML2; mastermind-like protein 2 isoform X1 [KO:K06061]
100386848  IL2; interleukin-2 [KO:K05429]
100386865  [KO:K06752]
100387059  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X4 [KO:K04348] [EC:3.1.3.16]
100387227  [KO:K06752]
100387686  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
100388148  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
100388189  IL2RG; cytokine receptor common subunit gamma precursor [KO:K05070]
100388493  RELA; transcription factor p65 isoform X1 [KO:K04735]
100388552  STAT5B; signal transducer and activator of transcription 5B isoform X1 [KO:K11224]
100388917  STAT5A; signal transducer and activator of transcription 5A isoform X1 [KO:K11223]
100388952  IFNG; interferon gamma precursor [KO:K04687]
100389441  GATA3; trans-acting T-cell-specific transcription factor GATA-3 isoform X1 [KO:K17895]
100389763  IFNGR2; interferon gamma receptor 2 [KO:K05133]
100390054  FOS; protein c-Fos [KO:K04379]
100390109  MAPK10; mitogen-activated protein kinase 10 isoform X7 [KO:K04440] [EC:2.7.11.24]
100390258  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
100390285  STAT6; signal transducer and activator of transcription 6 [KO:K11225]
100390885  RUNX3; runt-related transcription factor 3 isoform X1 [KO:K09279]
100390922  [KO:K07360] [EC:2.7.10.2]
100390939  MAML1; mastermind-like protein 1 [KO:K06061]
100392721  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
100392986  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
100393096  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X2 [KO:K07209] [EC:2.7.11.10]
100393268  NFKBIE; NF-kappa-B inhibitor epsilon [KO:K05872]
100393796  IL12RB2; interleukin-12 receptor subunit beta-2 [KO:K05064]
100393852  NOTCH2; neurogenic locus notch homolog protein 2 isoform X1 [KO:K20994]
100394910  IL2RB; interleukin-2 receptor subunit beta [KO:K05069]
100395403  IL12B; interleukin-12 subunit beta [KO:K05425]
100396611  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
100396967  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
100397491  JAK3; tyrosine-protein kinase JAK3 isoform X1 [KO:K11218] [EC:2.7.10.2]
100397497  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 [KO:K01116] [EC:3.1.4.11]
100397732  [KO:K06752]
100398335  DLL3; delta-like protein 3 isoform X2 [KO:K06051]
100399291  IL12RB1; interleukin-12 receptor subunit beta-1 isoform X1 [KO:K05063]
100400411  JUN; transcription factor Jun [KO:K04448]
100400700  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
100400742  RBPJL; recombining binding protein suppressor of hairless-like protein isoform X1 [KO:K06053]
100401630  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
100402266  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
100402355  STAT4; signal transducer and activator of transcription 4 isoform X1 [KO:K11222]
100403762  RBPJ; recombining binding protein suppressor of hairless isoform X4 [KO:K06053]
100403776  DLL1; delta-like protein 1 [KO:K06051]
100403944  CD3E; T-cell surface glycoprotein CD3 epsilon chain precursor [KO:K06451]
100404313  CD3D; T-cell surface glycoprotein CD3 delta chain isoform X2 [KO:K06450]
100404377  MAPK14; mitogen-activated protein kinase 14 isoform X2 [KO:K04441] [EC:2.7.11.24]
100404679  [KO:K06452]
100404815  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100405093  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
100405187  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X2 [KO:K04446]
100405222  [KO:K06752]
100405583  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
100406536  IL4; interleukin-4 precursor [KO:K05430]
100406669  IL12A; interleukin-12 subunit alpha [KO:K05406]
100406801  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
100406899  IL13; interleukin-13 precursor [KO:K05435]
100407348  JAG2; protein jagged-2 [KO:K21635]
100407630  IL5; interleukin-5 precursor [KO:K05428]
100407771  CAJA-DMA; HLA class II histocompatibility antigen, DM alpha chain [KO:K06752]
100408132  CAJA-DOA; HLA class II histocompatibility antigen, DO alpha chain [KO:K06752]
100408189  DLL4; delta-like protein 4 [KO:K06051]
100408503  CAJA-DPB1; HLA class II histocompatibility antigen, DP beta 1 chain isoform X3 [KO:K06752]
100408512  NFKBIB; NF-kappa-B inhibitor beta isoform X1 [KO:K02581]
100408524  TBX21; T-box transcription factor TBX21 isoform X2 [KO:K10166]
100408994  NOTCH3; neurogenic locus notch homolog protein 3 isoform X1 [KO:K20995]
100409044  [KO:K10784]
100410584  LCK; tyrosine-protein kinase Lck isoform X1 [KO:K05856] [EC:2.7.10.2]
100411388  [KO:K06752]
100412016  IL2RA; interleukin-2 receptor subunit alpha precursor [KO:K05068]
100412639  IL4R; interleukin-4 receptor subunit alpha precursor [KO:K05071]
100412691  CAJA-DMB; HLA class II histocompatibility antigen, DM beta chain isoform X1 [KO:K06752]
100413251  JAK2; tyrosine-protein kinase JAK2 [KO:K04447] [EC:2.7.10.2]
100413648  CAJA-DPA1; HLA class II histocompatibility antigen, DP alpha 1 chain [KO:K06752]
100413881  MAML3; mastermind-like protein 3 isoform X1 [KO:K06061]
100414442  LAT; linker for activation of T-cells family member 1 isoform X1 [KO:K07362]
100414856  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
100414977  JAG1; protein jagged-1 isoform X1 [KO:K06052]
100415241  PRKCQ; protein kinase C theta type isoform X2 [KO:K18052] [EC:2.7.11.13]
100415321  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
100896470  [KO:K10785]
100896810  CD247; T-cell surface glycoprotein CD3 zeta chain isoform X1 [KO:K06453]
100896987  [KO:K10785]
103795708  NOTCH1; neurogenic locus notch homolog protein 1 isoform X1 [KO:K02599]
128931734  [KO:K06752]
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
cjc04010  MAPK signaling pathway
cjc04020  Calcium signaling pathway
cjc04064  NF-kappa B signaling pathway
cjc04330  Notch signaling pathway
cjc04514  Cell adhesion molecule (CAM) interaction
cjc04630  JAK-STAT signaling pathway
cjc04660  T cell receptor signaling pathway
KO pathway
ko04658   

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