Cytokines and transcription factors that regulate T helper cell differentiation: new players and new insights.
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. T helper (TH)1 cells produce interferon (IFN)-gamma, 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-gamma. 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.
Agnello
Davide
D
Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Building 10, Room 9N262, 10 Center Drive, MSC 1820, Bethesda, Maryland 20802-1820, USA.
Lankford
Carla S R
CS
Bream
Jay
J
Morinobu
Akio
A
Gadina
Massimo
M
O'Shea
John J
JJ
Frucht
David M
DM
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D016207:Cytokines / Q000502:physiology*; D006801:Humans; D015398:Signal Transduction / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology*; D014157:Transcription Factors / Q000502:physiology*
D016207:Cytokines; D014157:Transcription Factors