KEGG   PATHWAY: mbez04658
Entry
mbez04658                   Pathway                                
Name
Th1 and Th2 cell differentiation - Moschus berezovskii (Chinese forest musk deer)
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
mbez04658  Th1 and Th2 cell differentiation
mbez04658

Other DBs
GO: 0045063 0045064
Organism
Moschus berezovskii (Chinese forest musk deer) [GN:mbez]
Gene
129563052  DLL4; delta-like protein 4 [KO:K06051]
129546215  DLL3; delta-like protein 3 [KO:K06051]
129561086  DLL1; delta-like protein 1 [KO:K06051]
129558457  NOTCH3; neurogenic locus notch homolog protein 3 [KO:K20995]
129542575  MAML3; mastermind-like protein 3 isoform X1 [KO:K06061]
129559299  MAML1; mastermind-like protein 1 [KO:K06061]
129554264  MAML2; mastermind-like protein 2 [KO:K06061]
129564112  RBPJL; recombining binding protein suppressor of hairless-like protein isoform X1 [KO:K06053]
129561785  RBPJ; recombining binding protein suppressor of hairless isoform X1 [KO:K06053]
129562101  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
129548767  RELA; transcription factor p65 [KO:K04735]
129536468  IFNG; interferon gamma [KO:K04687]
129560886  IFNGR1; interferon gamma receptor 1 isoform X1 [KO:K05132]
129552631  IFNGR2; interferon gamma receptor 2 [KO:K05133]
129541821  JAK1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
129557601  JAK2; tyrosine-protein kinase JAK2 [KO:K04447] [EC:2.7.10.2]
129537915  STAT1; signal transducer and activator of transcription 1-alpha/beta [KO:K11220]
129551055  IL12A; interleukin-12 subunit alpha [KO:K05406]
129558692  IL12B; interleukin-12 subunit beta isoform X1 [KO:K05425]
129559429  IL12RB1; interleukin-12 receptor subunit beta-1 isoform X1 [KO:K05063]
129540477  IL12RB2; interleukin-12 receptor subunit beta-2 [KO:K05064]
129558611  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
129538285  STAT4; signal transducer and activator of transcription 4 [KO:K11222]
129537311  TBX21; T-box transcription factor TBX21 [KO:K10166]
129538325  RUNX3; runt-related transcription factor 3 isoform X1 [KO:K09279]
129543058  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
129543060  HLA class II histocompatibility antigen, DR alpha chain [KO:K06752]
129543211  rano class II histocompatibility antigen, A beta chain-like [KO:K06752]
129543214  HLA class II histocompatibility antigen, DM alpha chain isoform X1 [KO:K06752]
129543215  SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like [KO:K06752]
129543218  HLA class II histocompatibility antigen, DQ alpha 2 chain-like isoform X1 [KO:K06752]
129543236  HLA class II histocompatibility antigen, DM beta chain isoform X1 [KO:K06752]
129543392  SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like [KO:K06752]
129543470  HLA class II histocompatibility antigen, DO alpha chain-like [KO:K06752]
129543574  SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like [KO:K06752]
129543605  boLa class II histocompatibility antigen, DQB*0101 beta chain-like [KO:K06752]
129543630  boLa class II histocompatibility antigen, DQB*0101 beta chain [KO:K06752]
129543645  DLA class II histocompatibility antigen, DR-1 beta chain-like isoform X1 [KO:K06752]
129543651  HLA class II histocompatibility antigen, DO beta chain [KO:K06752]
129543663  boLa class II histocompatibility antigen, DQB*0101 beta chain-like [KO:K06752]
129557775  boLa class II histocompatibility antigen, DQB*0101 beta chain-like [KO:K06752]
129547512  SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like [KO:K06752]
129547513  boLa class II histocompatibility antigen, DQB*0101 beta chain-like [KO:K06752]
129547514  SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like [KO:K06752]
129536212  CD4; T-cell surface glycoprotein CD4 isoform X1 [KO:K06454]
129537772  LCK; tyrosine-protein kinase Lck [KO:K05856] [EC:2.7.10.2]
129553777  T-cell surface glycoprotein CD3 epsilon chain [KO:K06451]
129553779  T-cell surface glycoprotein CD3 gamma chain [KO:K06452]
129540464  CD247; T-cell surface glycoprotein CD3 zeta chain [KO:K06453]
129553778  T-cell surface glycoprotein CD3 delta chain [KO:K06450]
129539813  tyrosine-protein kinase ZAP-70 [KO:K07360] [EC:2.7.10.2]
129545479  LAT; linker for activation of T-cells family member 1 isoform X1 [KO:K07362]
129563552  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
129556888  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
129562133  PPP3CA; protein phosphatase 3 catalytic subunit alpha isoform X1 [KO:K04348] [EC:3.1.3.16]
129555711  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
129539040  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
129549652  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
129535111  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
129546977  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
129556841  PRKCQ; protein kinase C theta type [KO:K18052] [EC:2.7.11.13]
129555451  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
129549430  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
129564146  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
129550521  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
129546849  NFKBIB; NF-kappa-B inhibitor beta isoform X1 [KO:K02581]
129543249  NFKBIE; NF-kappa-B inhibitor epsilon isoform X1 [KO:K05872]
129542485  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
129545501  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
129563123  FOS; protein c-Fos [KO:K04379]
129537071  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
129537073  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
129543604  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
129543888  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
129545108  mitogen-activated protein kinase 14-like [KO:K04441] [EC:2.7.11.24]
129559467  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
129561625  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
129555633  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
129540610  JUN; transcription factor Jun [KO:K04448]
129542297  IL2; interleukin-2 [KO:K05429]
129556783  IL2RA; interleukin-2 receptor subunit alpha isoform X1 [KO:K05068]
129536097  interleukin-2 receptor subunit beta-like [KO:K05069]
129537055  IL2RB; interleukin-2 receptor subunit beta [KO:K05069]
129564419  IL2RG; cytokine receptor common subunit gamma [KO:K05070]
129559327  JAK3; tyrosine-protein kinase JAK3 isoform X1 [KO:K11218] [EC:2.7.10.2]
129544422  STAT5A; signal transducer and activator of transcription 5A [KO:K11223]
129544423  STAT5B; signal transducer and activator of transcription 5B isoform X1 [KO:K11224]
129558702  IL4; interleukin-4 [KO:K05430]
129545473  IL4R; interleukin-4 receptor subunit alpha [KO:K05071]
129536419  STAT6; signal transducer and activator of transcription 6 isoform X1 [KO:K11225]
129556937  GATA3; trans-acting T-cell-specific transcription factor GATA-3 isoform X1 [KO:K17895]
129558706  IL5; interleukin-5 [KO:K05428]
129558703  IL13; interleukin-13 [KO:K05435]
129547243  MAF; transcription factor Maf [KO:K09035]
129556496  JAG1; LOW QUALITY PROTEIN: protein jagged-1 [KO:K06052]
129550716  JAG2; protein jagged-2 isoform X1 [KO:K21635]
129539195  NOTCH1; neurogenic locus notch homolog protein 1 [KO:K02599]
129541080  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
mbez04010  MAPK signaling pathway
mbez04020  Calcium signaling pathway
mbez04064  NF-kappa B signaling pathway
mbez04330  Notch signaling pathway
mbez04514  Cell adhesion molecules
mbez04630  JAK-STAT signaling pathway
mbez04660  T cell receptor signaling pathway
KO pathway
ko04658   
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