title: Complex interactions of transcription factors in mediating cytokine biology in T cells.
abstract: T-helper (Th) cells play critical roles within the mammalian immune system, and the differentiation of naive CD4(+) T cells into distinct T-helper subsets is critical for normal immunoregulation and host defense. These carefully regulated differentiation processes are controlled by networks of cytokines, transcription factors, and epigenetic modifications, resulting in the generation of multiple CD4(+) T-cell subsets, including Th1, Th2, Th9, Th17, Treg, and Tfh cells. In this review, we discuss the roles of transcription factors in determining the specific type of differentiation and in particular the role of interleukin-2 (IL-2) in promoting or inhibiting Th differentiation. In addition to discussing master regulators and subset-specific transcription factors for distinct T-helper cell populations, we focus on signal transducer and activator of transcription (STAT) proteins and on the cooperative action of interferon regulatory factor 4 (IRF4) with activator protein 1 (AP-1) family proteins and STAT3 in the assembly of complexes that broadly influence T-cell differentiation.
authors.affiliation: Laboratory of Molecular Immunology and Immunology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.forename: Rosanne
authors.initials: R
authors.lastname: Spolski
authors.forename: Wei
authors.initials: W
authors.lastname: Liao
authors.forename: Warren J
authors.initials: WJ
authors.lastname: Leonard
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D016207:Cytokines / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology*; D011485:Protein Binding; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D016207:Cytokines; D007376:Interleukin-2; D014157:Transcription Factors
keywords: T cells; Th1/Th2/Th17 cells; cell differentiation; cytokines; gene regulation; transcription factors