title: Signal transduction pathways and transcriptional regulation in Th17 cell differentiation.
abstract: Over the last decade, our understanding of helper/effector T cell differentiation has changed dramatically. The discovery of interleukin (IL-)17-producing T cells (Th17) and other subsets has changed our view of T cell-mediated immunity. Characterization of the signaling pathways involved in the Th17 commitment has provided exciting new insights into the differentiation of CD4+ T cells. Importantly, the emerging data on conversion among polarized T helper cells have raised the question how we should view such concepts as T cell lineage commitment, terminal differentiation and plasticity. In this review, we will discuss the current understanding of the signaling pathways, molecular interactions, and transcriptional and epigenetic events that contribute to Th17 differentiation and acquisition of effector functions.
authors.affiliation: Lymphocyte Cell Biology Section, Molecular Immunology and Inflammation Branch, National Institutes of Arthritis, and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA. hiraharak@mail.nih.gov
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Hirahara
authors.forename: Kamran
authors.initials: K
authors.lastname: Ghoreschi
authors.forename: Arian
authors.initials: A
authors.lastname: Laurence
authors.forename: Xiang-Ping
authors.initials: XP
authors.lastname: Yang
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kanno
authors.forename: John J
authors.initials: JJ
authors.lastname: O'Shea
mesh_terms: D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000502:physiology; D002454:Cell Differentiation / Q000276:immunology*; D019070:Cell Lineage / Q000276:immunology; D050657:Core Binding Factor alpha Subunits / Q000502:physiology; D057890:Epigenomics; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis; D053759:Interleukin-23 / Q000502:physiology; D015850:Interleukin-6 / Q000502:physiology; D008246:Lysophospholipids / Q000502:physiology; D051379:Mice; D035683:MicroRNAs / Q000502:physiology; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000502:physiology; D047488:Retinoid X Receptors / Q000502:physiology; D050796:STAT3 Transcription Factor / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology*; D051899:Smad2 Protein / Q000502:physiology; D013110:Sphingosine / Q000031:analogs & derivatives / Q000502:physiology; D058504:Th17 Cells / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000502:physiology
chemical_list: C099359:BATF protein, human; D050976:Basic-Leucine Zipper Transcription Factors; D050657:Core Binding Factor alpha Subunits; D020381:Interleukin-17; D053759:Interleukin-23; D015850:Interleukin-6; D008246:Lysophospholipids; D035683:MicroRNAs; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D047488:Retinoid X Receptors; D050796:STAT3 Transcription Factor; D051899:Smad2 Protein; D016212:Transforming Growth Factor beta; C060506:sphingosine 1-phosphate; D013110:Sphingosine