The role and modulation of CCR6+ Th17 cell populations in rheumatoid arthritis

Sandra M.J. Paulissen, Jan Piet van Hamburg, Wendy Dankers, Erik Lubberts

Research output: Contribution to journalReview ArticleResearchpeer-review

67 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)43-53
Number of pages11
JournalCytokine
Volume74
Issue number1
DOIs
Publication statusPublished - 1 Jul 2015
Externally publishedYes

Keywords

  • Autoimmune disease
  • CCR6
  • Plasticity
  • Rheumatoid arthritis
  • Th17

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