KEGG   PATHWAY: mlf04658
Entry
mlf04658                    Pathway                                
Name
Th1 and Th2 cell differentiation - Myotis lucifugus (little brown bat)
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
mlf04658  Th1 and Th2 cell differentiation
mlf04658

Other DBs
GO: 0045063 0045064
Organism
Myotis lucifugus (little brown bat) [GN:mlf]
Gene
102418841  DLL1; LOW QUALITY PROTEIN: delta-like protein 1 [KO:K06051]
102440726  DLL3; LOW QUALITY PROTEIN: delta-like protein 3 [KO:K06051]
102438421  DLL4; delta-like protein 4 [KO:K06051]
102424223  NOTCH3; LOW QUALITY PROTEIN: neurogenic locus notch homolog protein 3 [KO:K20995]
102421417  MAML3; LOW QUALITY PROTEIN: mastermind-like protein 3 [KO:K06061]
102427879  MAML2; mastermind-like protein 2 [KO:K06061]
102422930  MAML1; mastermind-like protein 1 [KO:K06061]
102441013  RBPJ; recombining binding protein suppressor of hairless isoform X1 [KO:K06053]
102428796  RBPJL; LOW QUALITY PROTEIN: recombining binding protein suppressor of hairless-like protein [KO:K06053]
102435748  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
102424236  RELA; transcription factor p65 [KO:K04735]
102438946  IFNG; interferon gamma [KO:K04687]
102440031  IFNGR1; interferon gamma receptor 1 isoform X1 [KO:K05132]
102422535  IFNGR2; interferon gamma receptor 2 [KO:K05133]
102442353  JAK1; tyrosine-protein kinase JAK1 isoform X1 [KO:K11217] [EC:2.7.10.2]
102420466  JAK2; LOW QUALITY PROTEIN: tyrosine-protein kinase JAK2 [KO:K04447] [EC:2.7.10.2]
102424662  STAT1; signal transducer and activator of transcription 1-alpha/beta isoform X1 [KO:K11220]
102431058  IL12A; interleukin-12 subunit alpha [KO:K05406]
102435627  IL12B; interleukin-12 subunit beta [KO:K05425]
102421801  IL12RB1; interleukin-12 receptor subunit beta-1 [KO:K05063]
102425026  IL12RB2; interleukin-12 receptor subunit beta-2 [KO:K05064]
102433832  TYK2; non-receptor tyrosine-protein kinase TYK2 isoform X1 [KO:K11219] [EC:2.7.10.2]
102424971  STAT4; signal transducer and activator of transcription 4 [KO:K11222]
102442910  TBX21; LOW QUALITY PROTEIN: T-box transcription factor TBX21 [KO:K10166]
102425510  RUNX3; LOW QUALITY PROTEIN: runt-related transcription factor 3 [KO:K09279]
102433442  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
111822996  HLA class II histocompatibility antigen, DQ beta 1 chain-like [KO:K06752]
111823581  HLA class II histocompatibility antigen, DQ beta 1 chain-like [KO:K06752]
102424361  HLA class II histocompatibility antigen, DQ alpha 2 chain-like [KO:K06752]
102424046  boLa class II histocompatibility antigen, DQB*0101 beta chain-like [KO:K06752]
102426046  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
102417581  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
102417899  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
102418225  HLA class II histocompatibility antigen, DRB1-4 beta chain-like [KO:K06752]
102416953  SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like [KO:K06752]
102421254  HLA class II histocompatibility antigen, DM beta chain [KO:K06752]
102423761  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
102441293  SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like [KO:K06752]
102418131  HLA class II histocompatibility antigen, DR alpha chain-like [KO:K06752]
102434058  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
102434372  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
111824054  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
102443188  HLA class II histocompatibility antigen, DQ alpha 2 chain-like [KO:K06752]
102431574  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
102431885  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
102417382  SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like [KO:K06752]
102431149  HLA class II histocompatibility antigen, DRB1-9 beta chain-like [KO:K06752]
102417268  HLA class II histocompatibility antigen, DQ beta 1 chain-like [KO:K06752]
102439327  SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like [KO:K06752]
106694679  SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like [KO:K06752]
102426241  HLA class II histocompatibility antigen, DQ alpha 2 chain-like [KO:K06752]
102423747  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
102433751  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
106695222  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
102422459  HLA class II histocompatibility antigen, DM alpha chain [KO:K06752]
102419180  SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like [KO:K06752]
102441506  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
102428157  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
102431769  HLA class II histocompatibility antigen, DRB1-4 beta chain-like [KO:K06752]
102418553  SLA class II histocompatibility antigen, DQ haplotype C beta chain-like [KO:K06752]
102419081  RLA class II histocompatibility antigen, DP alpha-1 chain-like [KO:K06752]
102423684  HLA class II histocompatibility antigen, DP beta 1 chain-like isoform X1 [KO:K06752]
102429593  H-2 class II histocompatibility antigen, E-S beta chain-like [KO:K06752]
102423144  SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like isoform X2 [KO:K06752]
102423440  boLa class II histocompatibility antigen, DQB*0101 beta chain-like [KO:K06752]
102423734  SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like [KO:K06752]
102425725  HLA class II histocompatibility antigen, DR alpha chain-like [KO:K06752]
102426355  SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like [KO:K06752]
102424057  DLA class II histocompatibility antigen, DR-1 beta chain-like isoform X1 [KO:K06752]
102424373  HLA class II histocompatibility antigen, DR beta 5 chain-like [KO:K06752]
102427698  CD4; T-cell surface glycoprotein CD4 [KO:K06454]
102428805  LCK; tyrosine-protein kinase Lck isoform X1 [KO:K05856] [EC:2.7.10.2]
102438976  CD3E; T-cell surface glycoprotein CD3 epsilon chain isoform X2 [KO:K06451]
102436522  CD3G; T-cell surface glycoprotein CD3 gamma chain [KO:K06452]
102427887  CD247; LOW QUALITY PROTEIN: T-cell surface glycoprotein CD3 zeta chain [KO:K06453]
102436834  CD3D; T-cell surface glycoprotein CD3 delta chain isoform X1 [KO:K06450]
102418755  LOW QUALITY PROTEIN: tyrosine-protein kinase ZAP-70-like [KO:K07360] [EC:2.7.10.2]
102438171  LAT; LOW QUALITY PROTEIN: linker for activation of T-cells family member 1 [KO:K07362]
102421330  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
102434410  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
102441003  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
102421207  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
102430192  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
102428803  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
102428507  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 [KO:K04446]
102441857  NFATC2; LOW QUALITY PROTEIN: nuclear factor of activated T-cells, cytoplasmic 2 [KO:K17332]
102426111  NFATC3; nuclear factor of activated T-cells, cytoplasmic 3 isoform X1 [KO:K17333]
102425850  PRKCQ; protein kinase C theta type [KO:K18052] [EC:2.7.11.13]
102425603  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
102417312  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X4 [KO:K07209] [EC:2.7.11.10]
102436137  IKBKG; NF-kappa-B essential modulator isoform X3 [KO:K07210]
102422347  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
102418059  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
102420162  NFKBIE; NF-kappa-B inhibitor epsilon [KO:K05872]
102417755  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102422236  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102417433  FOS; proto-oncogene c-Fos [KO:K04379]
102438914  mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
102437934  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
102430582  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
102437455  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
102418507  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
102437415  JUN; LOW QUALITY PROTEIN: transcription factor AP-1 [KO:K04448]
102433200  IL2; interleukin-2 [KO:K05429]
102427118  IL2RA; interleukin-2 receptor subunit alpha [KO:K05068]
102420320  IL2RB; LOW QUALITY PROTEIN: interleukin-2 receptor subunit beta [KO:K05069]
102441989  IL2RG; cytokine receptor common subunit gamma [KO:K05070]
102428976  JAK3; tyrosine-protein kinase JAK3 [KO:K11218] [EC:2.7.10.2]
102423996  STAT5A; signal transducer and activator of transcription 5A isoform X1 [KO:K11223]
102424720  signal transducer and activator of transcription 5B isoform X1 [KO:K11224]
102437928  IL4; interleukin-4 [KO:K05430]
102423070  interleukin-4 receptor subunit alpha-like isoform X1 [KO:K05071]
102436222  IL4R; interleukin-4 receptor subunit alpha isoform X1 [KO:K05071]
102419724  STAT6; signal transducer and activator of transcription 6 isoform X2 [KO:K11225]
102439102  GATA3; LOW QUALITY PROTEIN: trans-acting T-cell-specific transcription factor GATA-3 [KO:K17895]
102430773  IL5; interleukin-5 [KO:K05428]
102437628  IL13; LOW QUALITY PROTEIN: interleukin-13 [KO:K05435]
102418962  JAG1; protein jagged-1 isoform X1 [KO:K06052]
106695521  NOTCH1; LOW QUALITY PROTEIN: neurogenic locus notch homolog protein 1 [KO:K02599]
102430236  NOTCH2; LOW QUALITY PROTEIN: neurogenic locus notch homolog protein 2 [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
mlf04010  MAPK signaling pathway
mlf04020  Calcium signaling pathway
mlf04064  NF-kappa B signaling pathway
mlf04330  Notch signaling pathway
mlf04514  Cell adhesion molecules
mlf04630  JAK-STAT signaling pathway
mlf04660  T cell receptor signaling pathway
KO pathway
ko04658   
LinkDB

DBGET integrated database retrieval system