Cytokines and transcription factors that regulate T helper cell differentiation: New players and new insights

Davide Agnello; Carla S.R. Lankford; Jay Bream; Akio Morinobu; Massimo Gadina; John J. O'Shea; David M. Frucht

doi:10.1023/A:1023381027062

Cytokines and transcription factors that regulate T helper cell differentiation: New players and new insights

Davide Agnello, Carla S.R. Lankford, Jay Bream, Akio Morinobu, Massimo Gadina, John J. O'Shea, David M. Frucht

Research output: Contribution to journal › Review article › peer-review

298 Scopus citations

Abstract

The differentiation of naive CD4⁺ T cells into subsets of T helper cells is a pivotal process with major implications for host defense and the pathogenesis of immune-mediated diseases. Though the basic paradigm was discovered more than 15 years ago, new discoveries continue to be made that offer fresh insights into the regulation of this process (1). T helper (T_H)1 cells produce interferon (IFN)-γ, promoting cell-mediated immunity and control of intracellular pathogens. We now know that T_H1 differentiation is regulated by transcription factors such as T-bet, Stat1, and Stat4, as well as cytokines such as IL-12, IL-23, IL-27, type I IFNs, and IFN-γ. In contrast, T_H2 cells produce IL-4, which promotes allergic responses and is important in host defense against helminths. The transcription factors Stat6, GATA-3, c-Maf, NFATs, and the cytokine IL-4 promote T_H2 differentiation. These key regulators of T_H differentiation are the subject of this review.

Original language	English (US)
Pages (from-to)	147-161
Number of pages	15
Journal	Journal of Clinical Immunology
Volume	23
Issue number	3
DOIs	https://doi.org/10.1023/A:1023381027062
State	Published - May 2003
Externally published	Yes

Keywords

Differentiation
GATA-3
IL-12
IL-23
IL-27
Interferon-γ
Interleukin (IL)-4
NFATs
Stat1
Stat4
Stat6
T helper (T) cells
T1 cells
T2 cells
c-Maf

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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title = "Cytokines and transcription factors that regulate T helper cell differentiation: New players and new insights",

abstract = "The differentiation of naive CD4+ T cells into subsets of T helper cells is a pivotal process with major implications for host defense and the pathogenesis of immune-mediated diseases. Though the basic paradigm was discovered more than 15 years ago, new discoveries continue to be made that offer fresh insights into the regulation of this process (1). T helper (TH)1 cells produce interferon (IFN)-γ, promoting cell-mediated immunity and control of intracellular pathogens. We now know that TH1 differentiation is regulated by transcription factors such as T-bet, Stat1, and Stat4, as well as cytokines such as IL-12, IL-23, IL-27, type I IFNs, and IFN-γ. In contrast, TH2 cells produce IL-4, which promotes allergic responses and is important in host defense against helminths. The transcription factors Stat6, GATA-3, c-Maf, NFATs, and the cytokine IL-4 promote TH2 differentiation. These key regulators of TH differentiation are the subject of this review.",

keywords = "Differentiation, GATA-3, IL-12, IL-23, IL-27, Interferon-γ, Interleukin (IL)-4, NFATs, Stat1, Stat4, Stat6, T helper (T) cells, T1 cells, T2 cells, c-Maf",

author = "Davide Agnello and Lankford, {Carla S.R.} and Jay Bream and Akio Morinobu and Massimo Gadina and O'Shea, {John J.} and Frucht, {David M.}",

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AU - Agnello, Davide

AU - Lankford, Carla S.R.

AU - Bream, Jay

AU - Morinobu, Akio

AU - Gadina, Massimo

AU - O'Shea, John J.

AU - Frucht, David M.

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N2 - The differentiation of naive CD4+ T cells into subsets of T helper cells is a pivotal process with major implications for host defense and the pathogenesis of immune-mediated diseases. Though the basic paradigm was discovered more than 15 years ago, new discoveries continue to be made that offer fresh insights into the regulation of this process (1). T helper (TH)1 cells produce interferon (IFN)-γ, promoting cell-mediated immunity and control of intracellular pathogens. We now know that TH1 differentiation is regulated by transcription factors such as T-bet, Stat1, and Stat4, as well as cytokines such as IL-12, IL-23, IL-27, type I IFNs, and IFN-γ. In contrast, TH2 cells produce IL-4, which promotes allergic responses and is important in host defense against helminths. The transcription factors Stat6, GATA-3, c-Maf, NFATs, and the cytokine IL-4 promote TH2 differentiation. These key regulators of TH differentiation are the subject of this review.

AB - The differentiation of naive CD4+ T cells into subsets of T helper cells is a pivotal process with major implications for host defense and the pathogenesis of immune-mediated diseases. Though the basic paradigm was discovered more than 15 years ago, new discoveries continue to be made that offer fresh insights into the regulation of this process (1). T helper (TH)1 cells produce interferon (IFN)-γ, promoting cell-mediated immunity and control of intracellular pathogens. We now know that TH1 differentiation is regulated by transcription factors such as T-bet, Stat1, and Stat4, as well as cytokines such as IL-12, IL-23, IL-27, type I IFNs, and IFN-γ. In contrast, TH2 cells produce IL-4, which promotes allergic responses and is important in host defense against helminths. The transcription factors Stat6, GATA-3, c-Maf, NFATs, and the cytokine IL-4 promote TH2 differentiation. These key regulators of TH differentiation are the subject of this review.

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KW - NFATs

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KW - Stat4

KW - Stat6

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KW - T2 cells

KW - c-Maf

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Cytokines and transcription factors that regulate T helper cell differentiation: New players and new insights

Abstract

Keywords

ASJC Scopus subject areas

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