title: Mechanisms underlying helper T-cell plasticity: implications for immune-mediated disease.
abstract: CD4 helper T cells are critical for proper immune cell homeostasis and host defense but are also major contributors to immune and inflammatory disease. Arising from a simple biphasic model of differentiation (ie, TH1 and TH2 cells). A bewildering number of fates seem possible for helper T cells. To what extent different helper cell subsets maintain their characteristic gene expression profiles or exhibit functional plasticity is a hotly debated topic. In this review we will discuss how the expression of "signature cytokines" and "master regulator" transcription factors do not neatly conform to a simple helper T-cell paradigm. Although this might seem confusing, the good news is that the newly recognized complexity fits better with our understanding of immunopathogenesis. Finally, we will discuss factors, including epigenetic regulation and metabolic alterations, that contribute to helper cell specificity and plasticity.
authors.affiliation: Molecular Immunology and Inflammation Branch, National Institutes of Arthritis, and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892-1930, USA.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Hirahara
authors.forename: Amanda
authors.initials: A
authors.lastname: Poholek
authors.forename: Golnaz
authors.initials: G
authors.lastname: Vahedi
authors.forename: Arian
authors.initials: A
authors.lastname: Laurence
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kanno
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Milner
authors.forename: John J
authors.initials: JJ
authors.lastname: O'Shea
mesh_terms: D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007154:Immune System Diseases / Q000209:etiology / Q000276:immunology* / Q000473:pathology*; D018448:Models, Immunological; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*
chemical_list: D016207:Cytokines