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

Cytokine. 2015 Jul;74(1):43-53. doi: 10.1016/j.cyto.2015.02.002. Epub 2015 Mar 28.


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.

Keywords: Autoimmune disease; CCR6; Plasticity; Rheumatoid arthritis; Th17.

Publication types

  • Review

MeSH terms

  • Arthritis, Rheumatoid / genetics
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / physiopathology
  • Arthritis, Rheumatoid / therapy
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / therapy
  • Cell Plasticity
  • Humans
  • Interleukin-17 / biosynthesis
  • Interleukin-17 / immunology
  • Microbiota
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / immunology
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism
  • Receptors, CCR6 / immunology
  • Receptors, CCR6 / metabolism*
  • Th17 Cells / immunology*
  • Th17 Cells / pathology
  • Th17 Cells / physiology


  • CCR6 protein, human
  • IL17A protein, human
  • Interleukin-17
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • RORC protein, human
  • Receptors, CCR6