KEGG   PATHWAY: rno04658
Entry
rno04658                    Pathway                                
Name
Th1 and Th2 cell differentiation - Rattus norvegicus (rat)
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
rno04658  Th1 and Th2 cell differentiation
rno04658

Other DBs
GO: 0045063 0045064
Organism
Rattus norvegicus (rat) [GN:rno]
Gene
114125  Dll3; delta-like protein 3 precursor [KO:K06051]
311332  Dll4; delta-like protein 4 precursor [KO:K06051]
84010  Dll1; delta-like protein 1 precursor [KO:K06051]
56761  Notch3; neurogenic locus notch homolog protein 3 precursor [KO:K20995]
689844  Maml2; mastermind-like protein 2 isoform X1 [KO:K06061]
310405  Maml3; mastermind-like protein 3 [KO:K06061]
303101  Maml1; mastermind-like protein 1 [KO:K06061]
362268  Rbpjl; recombining binding protein suppressor of hairless-like protein [KO:K06053]
679028  Rbpj; recombining binding protein suppressor of hairless isoform 1 [KO:K06053]
81736  Nfkb1; nuclear factor NF-kappa-B p105 subunit isoform 2 [KO:K02580]
309165  Rela; transcription factor p65 [KO:K04735]
25712  Ifng; interferon gamma precursor [KO:K04687]
116465  Ifngr1; interferon gamma receptor 1 precursor [KO:K05132]
360697  Ifngr2; interferon gamma receptor 2 precursor [KO:K05133]
84598  Jak1; tyrosine-protein kinase JAK1 [KO:K11217] [EC:2.7.10.2]
24514  Jak2; tyrosine-protein kinase JAK2 [KO:K04447] [EC:2.7.10.2]
25124  Stat1; signal transducer and activator of transcription 1-alpha/beta isoform beta [KO:K11220]
84405  Il12a; interleukin-12 subunit alpha precursor [KO:K05406]
64546  Il12b; interleukin-12 subunit beta precursor [KO:K05425]
171333  Il12rb1; interleukin-12 receptor subunit beta-1 precursor [KO:K05063]
171334  Il12rb2; interleukin-12 receptor subunit beta-2 precursor [KO:K05064]
100361294  Tyk2; non-receptor tyrosine-protein kinase TYK2 [KO:K11219] [EC:2.7.10.2]
367264  Stat4; signal transducer and activator of transcription 4 [KO:K11222]
303496  Tbx21; T-box transcription factor TBX21 [KO:K10166]
156726  Runx3; runt-related transcription factor 3 isoform 2 [KO:K09279]
294274  RT1-DMa; RT1 class II, DM alpha precursor [KO:K06752]
294273  RT1-DMb; RT1 class II, DM beta precursor [KO:K06752]
24984  RT1-DOa; RT1 class II, locus DOa precursor [KO:K06752]
24986  RT1-Ha; RT1 class II, locus Ha precursor [KO:K06752]
294269  RT1-Da; RT1 class II, locus Da precursor [KO:K06752]
294270  RT1-Db1; rano class II histocompatibility antigen, D-1 beta chain precursor [KO:K06752]
309621  RT1-Ba; rano class II histocompatibility antigen, B alpha chain precursor [KO:K06752]
309622  RT1-Bb; rano class II histocompatibility antigen, B-1 beta chain precursor [KO:K06752]
365542  RT1-DOb; RT1 class II, DO beta isoform 1 [KO:K06752]
24981  RT1-Db2; RT1 class II, locus Db2 precursor [KO:K06752]
24932  Cd4; T-cell surface glycoprotein CD4 precursor [KO:K06454]
313050  Lck; proto-oncogene tyrosine-protein kinase LCK [KO:K05856] [EC:2.7.10.2]
315609  Cd3e; T-cell surface glycoprotein CD3 epsilon chain precursor [KO:K06451]
300678  Cd3g; T-cell surface glycoprotein CD3 gamma chain precursor [KO:K06452]
25300  Cd247; T-cell surface glycoprotein CD3 zeta chain isoform 2 precursor [KO:K06453]
25710  Cd3d; T-cell surface glycoprotein CD3 delta chain precursor [KO:K06450]
301348  Zap70; tyrosine-protein kinase ZAP-70 [KO:K07360] [EC:2.7.10.2]
81511  Lat; linker for activation of T-cells family member 1 [KO:K07362]
25738  Plcg1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 [KO:K01116] [EC:3.1.4.11]
24674  Ppp3ca; protein phosphatase 3 catalytic subunit alpha [KO:K04348] [EC:3.1.3.16]
24675  Ppp3cb; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform [KO:K04348] [EC:3.1.3.16]
171378  Ppp3cc; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform [KO:K04348] [EC:3.1.3.16]
29748  Ppp3r1; calcineurin subunit B type 1 [KO:K06268]
29749  Ppp3r2; calcineurin subunit B type 2 [KO:K06268]
100361818  Nfatc1; nuclear factor of activated T-cells, cytoplasmic 1 isoform 1 [KO:K04446]
311658  Nfatc2; nuclear factor of activated T-cells, cytoplasmic 2 [KO:K17332]
361400  Nfatc3; nuclear factor of activated T-cells, cytoplasmic 3 [KO:K17333]
85420  Prkcq; protein kinase C theta type [KO:K18052] [EC:2.7.11.13]
309361  Chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
84351  Ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
309295  Ikbkg; NF-kappa-B essential modulator [KO:K07210]
25493  Nfkbia; NF-kappa-B inhibitor alpha [KO:K04734]
81525  Nfkbib; NF-kappa-B inhibitor beta [KO:K02581]
316241  Nfkbie; NF-kappa-B inhibitor epsilon [KO:K05872]
116590  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
50689  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
314322  Fos; protein c-Fos [KO:K04379]
81649  Mapk14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
60352  Mapk12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
29513  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
689314  Mapk11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
25272  Mapk10; mitogen-activated protein kinase 10 isoform 2 [KO:K04440] [EC:2.7.11.24]
50658  Mapk9; mitogen-activated protein kinase 9 isoform 2 [KO:K04440] [EC:2.7.11.24]
116554  Mapk8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
24516  Jun; transcription factor Jun [KO:K04448]
116562  Il2; interleukin-2 precursor [KO:K05429]
25704  Il2ra; interleukin-2 receptor subunit alpha precursor [KO:K05068]
25746  Il2rb; interleukin-2 receptor subunit beta precursor [KO:K05069]
140924  Il2rg; cytokine receptor common subunit gamma precursor [KO:K05070]
25326  Jak3; tyrosine-protein kinase JAK3 [KO:K11218] [EC:2.7.10.2]
24918  Stat5a; signal transducer and activator of transcription 5A [KO:K11223]
25126  Stat5b; signal transducer and activator of transcription 5B [KO:K11224]
287287  Il4; interleukin-4 precursor [KO:K05430]
25084  Il4r; interleukin-4 receptor subunit alpha precursor [KO:K05071]
362896  Stat6; signal transducer and activator of transcription 6 [KO:K11225]
85471  Gata3; trans-acting T-cell-specific transcription factor GATA-3 [KO:K17895]
24497  Il5; interleukin-5 precursor [KO:K05428]
116553  Il13; interleukin-13 precursor [KO:K05435]
54267  Maf; transcription factor Maf [KO:K09035]
29146  Jag1; protein jagged-1 precursor [KO:K06052]
29147  Jag2; protein jagged-2 isoform 2 [KO:K21635]
25496  Notch1; neurogenic locus notch homolog protein 1 precursor [KO:K02599]
29492  Notch2; neurogenic locus notch homolog protein 2 precursor [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
rno04010  MAPK signaling pathway
rno04020  Calcium signaling pathway
rno04064  NF-kappa B signaling pathway
rno04330  Notch signaling pathway
rno04514  Cell adhesion molecules
rno04630  JAK-STAT signaling pathway
rno04660  T cell receptor signaling pathway
KO pathway
ko04658   
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