Entry Name Th1 and Th2 cell differentiation
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 systemBRITE hierarchy
Pathway map ko04658 Th1 and Th2 cell differentiation
Other DBs Orthology K01116 PLCG1; phosphatidylinositol phospholipase C, gamma-1 [EC:3.1.4.11 ]
K02580 NFKB1; nuclear factor NF-kappa-B p105 subunit
K02581 NFKBIB; NF-kappa-B inhibitor beta
K04348 PPP3C, CNA; serine/threonine-protein phosphatase 2B catalytic subunit [EC:3.1.3.16 ]
K04379 FOS; proto-oncogene protein c-fos
K04440 JNK; mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24 ]
K04446 NFATC1, NFAT2, NFATC; nuclear factor of activated T-cells, cytoplasmic 1
K04448 JUN; transcription factor AP-1
K04467 IKBKA, IKKA, CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:2.7.11.10 ]
K04734 NFKBIA; NF-kappa-B inhibitor alpha
K04735 RELA; transcription factor p65
K05063 IL12RB1, CD212; interleukin 12 receptor beta-1
K05064 IL12RB2; interleukin 12 receptor beta-2
K05068 IL2RA, CD25; interleukin 2 receptor alpha
K05069 IL2RB, CD122; interleukin 2 receptor beta
K05070 IL2RG, CD132; interleukin 2 receptor gamma
K05071 IL4R, CD124; interleukin 4 receptor
K05132 IFNGR1, CD119; interferon gamma receptor 1
K05133 IFNGR2; interferon gamma receptor 2
K05856 LCK; lymphocyte cell-specific protein tyrosine kinase [EC:2.7.10.2 ]
K05872 NFKBIE; NF-kappa-B inhibitor epsilon
K06053 RBPSUH, RBPJK; recombining binding protein suppressor of hairless
K06268 PPP3R, CNB; serine/threonine-protein phosphatase 2B regulatory subunit
K06450 CD3D; T-cell surface glycoprotein CD3 delta chain
K06451 CD3E; T-cell surface glycoprotein CD3 epsilon chain
K06452 CD3G; T-cell surface glycoprotein CD3 gamma chain
K06453 CD3Z, CD247; CD3Z antigen, zeta polypeptide
K06454 CD4; T-cell surface glycoprotein CD4
K06752 MHC2; MHC class II antigen
K07209 IKBKB, IKKB; inhibitor of nuclear factor kappa-B kinase subunit beta [EC:2.7.11.10 ]
K07210 IKBKG, IKKG, NEMO; inhibitor of nuclear factor kappa-B kinase subunit gamma
K07362 LAT; linker for activation of T cells family member 1
K09035 CMAF, MAF; transcription factor Maf
K09279 RUNX3, AML2; runt-related transcription factor 3
K10166 TBX21; T-box protein 21
K10784 TRAV; T cell receptor alpha chain V region
K10785 TRBV; T-cell receptor beta chain V region
K11220 STAT1; signal transducer and activator of transcription 1
K11222 STAT4; signal transducer and activator of transcription 4
K11223 STAT5A; signal transducer and activator of transcription 5A
K11224 STAT5B; signal transducer and activator of transcription 5B
K11225 STAT6; signal transducer and activator of transcription 6
K17332 NFATC2, NFAT1, NFATP; nuclear factor of activated T-cells, cytoplasmic 2
K17333 NFATC3, NFAT4; nuclear factor of activated T-cells, cytoplasmic 3
K17895 GATA3; GATA-binding protein 3
Compound C01245 D-myo-Inositol 1,4,5-trisphosphate
Reference Authors Amsen D, Spilianakis CG, Flavell RA
Title How are T(H)1 and T(H)2 effector cells made?
Journal Reference Authors Knosp CA, Johnston JA
Title Regulation of CD4+ T-cell polarization by suppressor of cytokine signalling proteins.
Journal Reference Authors Dong C, Flavell RA
Title Control of T helper cell differentiation--in search of master genes.
Journal Reference Authors O'Garra A, Arai N
Title The molecular basis of T helper 1 and T helper 2 cell differentiation.
Journal Reference 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 Reference Authors Kolls JK
Title CD4(+) T-cell subsets and host defense in the lung.
Journal Reference Authors Zhu J, Paul WE
Title Peripheral CD4+ T-cell differentiation regulated by networks of cytokines and transcription factors.
Journal Reference Authors Wilson CB, Rowell E, Sekimata M
Title Epigenetic control of T-helper-cell differentiation.
Journal Reference Authors Callard RE, Yates AJ
Title Immunology and mathematics: crossing the divide.
Journal Reference Authors Lazarevic V, Glimcher LH, Lord GM
Title T-bet: a bridge between innate and adaptive immunity.
Journal Reference Authors Weigmann B, Neurath MF
Title T-bet and mucosal Th1 responses in the gastrointestinal tract.
Journal Reference Authors Adamson AS, Collins K, Laurence A, O'Shea JJ
Title The Current STATus of lymphocyte signaling: new roles for old players.
Journal Reference Authors Zhu J
Title Transcriptional regulation of Th2 cell differentiation.
Journal Reference 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 Reference 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 Reference Authors Amsen D, Antov A, Flavell RA
Title The different faces of Notch in T-helper-cell differentiation.
Journal Reference Authors Pahan K, Mondal S
Title Crosstalk between Nitric Oxide and T helper cells.
Journal J Clin Cell Immunol 3:e109 (2012)
Reference Authors Schmidt A, Oberle N, Krammer PH
Title Molecular mechanisms of treg-mediated T cell suppression.
Journal Related ko04064 NF-kappa B signaling pathway
ko04660 T cell receptor signaling pathway
