title: The role and modulation of CCR6+ Th17 cell populations in rheumatoid arthritis.
abstract: The IL-17A producing T-helper-17 (Th17) cell population plays a major role in rheumatoid arthritis (RA) pathogenesis and has gained wide interest as treatment target. IL-17A expressing Th cells are characterized by the expression of the chemokine receptor CCR6 and the transcription factor RORC. In RA, CCR6+ Th cells were identified in peripheral blood, synovial fluid and inflamed synovial tissue. CCR6+ Th cells might drive the progression of an early inflammation towards a persistent arthritis. The CCR6+ Th cell population is heterogeneous and several subpopulations can be distinguished, including Th17, Th22, Th17.1 (also called non-classic Th1 cells), and unclassified or intermediate populations. Interestingly, some of these populations produce low levels of IL-17A but are still very pathogenic. Furthermore, the CCR6+ Th cells phenotype is unstable and plasticity exists between CCR6+ Th cells and T-regulatory (Treg) cells and within the CCR6+ Th cell subpopulations. In this review, characteristics of the different CCR6+ Th cell populations, their plasticity, and their potential impact on rheumatoid arthritis are discussed. Moreover, current approaches to target CCR6+ Th cells and future directions of research to find specific CCR6+ Th cell targets in the treatment of patients with RA and other CCR6+ Th cell mediated autoimmune diseases are highlighted.
authors.affiliation: Department of Rheumatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands; Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: Sandra M J
authors.initials: SM
authors.lastname: Paulissen
authors.affiliation: Department of Rheumatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands; Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: Jan Piet
authors.initials: JP
authors.lastname: van Hamburg
authors.affiliation: Department of Rheumatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands; Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: Wendy
authors.initials: W
authors.lastname: Dankers
authors.affiliation: Department of Rheumatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands; Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. Electronic address: e.lubberts@erasmusmc.nl.
authors.forename: Erik
authors.initials: E
authors.lastname: Lubberts
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy; D001327:Autoimmune Diseases / Q000276:immunology / Q000628:therapy; D000066670:Cell Plasticity; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis / Q000276:immunology; D064307:Microbiota; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000276:immunology / Q000378:metabolism; D054399:Receptors, CCR6 / Q000276:immunology / Q000378:metabolism*; D058504:Th17 Cells / Q000276:immunology* / Q000473:pathology / Q000502:physiology
chemical_list: C106311:CCR6 protein, human; C508717:IL17A protein, human; D020381:Interleukin-17; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C539900:RORC protein, human; D054399:Receptors, CCR6
keywords: Autoimmune disease; CCR6; Plasticity; Rheumatoid arthritis; Th17