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 system
BRITE hierarchy
Pathway map
ko04658 Th1 and Th2 cell differentiation
Ortholog table
Other DBs
Orthology
K06053 recombining binding protein suppressor of hairless
K02580 nuclear factor NF-kappa-B p105 subunit
K04735 transcription factor p65
K05132 interferon gamma receptor 1
K05133 interferon gamma receptor 2
K11220 signal transducer and activator of transcription 1
K05063 interleukin 12 receptor beta-1
K05064 interleukin 12 receptor beta-2
K11222 signal transducer and activator of transcription 4
K09279 runt-related transcription factor 3
K06454 T-cell surface glycoprotein CD4
K06451 T-cell surface glycoprotein CD3 epsilon chain
K06452 T-cell surface glycoprotein CD3 gamma chain
K10784 T cell receptor alpha chain V region
K10785 T-cell receptor beta chain V region
K06453 CD3Z antigen, zeta polypeptide
K06450 T-cell surface glycoprotein CD3 delta chain
K07362 linker for activation of T cells family member 1
K04348 serine/threonine-protein phosphatase 2B catalytic subunit [EC:3.1.3.16 ]
K06268 serine/threonine-protein phosphatase 2B regulatory subunit
K04446 nuclear factor of activated T-cells, cytoplasmic 1
K17332 nuclear factor of activated T-cells, cytoplasmic 2
K17333 nuclear factor of activated T-cells, cytoplasmic 3
K04467 inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:2.7.11.10 ]
K07209 inhibitor of nuclear factor kappa-B kinase subunit beta [EC:2.7.11.10 ]
K07210 inhibitor of nuclear factor kappa-B kinase subunit gamma
K04734 NF-kappa-B inhibitor alpha
K02581 NF-kappa-B inhibitor beta
K05872 NF-kappa-B inhibitor epsilon
K04379 proto-oncogene protein c-fos
K04440 mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24 ]
K04448 transcription factor AP-1
K05068 interleukin 2 receptor alpha
K05069 interleukin 2 receptor beta
K05070 interleukin 2 receptor gamma
K11223 signal transducer and activator of transcription 5A
K11224 signal transducer and activator of transcription 5B
K11225 signal transducer and activator of transcription 6
K09035 transcription factor Maf
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 pathway
ko04064 NF-kappa B signaling pathway
ko04660 T cell receptor signaling pathway
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