CD161 expression characterizes a sub-population of human regulatory T cells that produces IL-17 in a STAT3 dependent manner

Research output: Contribution to journalArticlepeer-review

106 Citations (Scopus)
239 Downloads (Pure)

Abstract

Treg cells are critical for the prevention of autoimmune diseases and are thus prime candidates for cell-based clinical therapy. However, human Treg cells are plastic, and are able to produce IL-17 under inflammatory conditions. Here, we identify and characterize the human Treg subpopulation that can be induced to produce IL-17 and identify its mechanisms. We confirm that a subpopulation of human Treg cells produces IL-17 in vitro when activated in the presence of IL-1, but not IL-6. IL-17 potential is restricted to population III (CD4(+)CD25(hi)CD127(lo)CD45RA(-)) Treg cells expressing the natural killer cell marker CD161. We show that these cells are functionally as suppressive and have similar phenotypic/molecular characteristics to other subpopulations of Treg cells and retain their suppressive function following IL-17 induction. Importantly, we find that IL-17 production is STAT3 dependent, with Treg cells from patients with STAT3 mutations unable to make IL-17. Finally, we show that CD161(+) population III Treg cells accumulate in inflamed joints of patients with inflammatory arthritis and are the predominant IL-17-producing Treg-cell population at these sites. As IL-17 production from this Treg-cell subpopulation is not accompanied by a loss of regulatory function, in the context of cell therapy, exclusion of these cells from the cell product may not be necessary.

Original languageEnglish
Pages (from-to)2043-2054
Number of pages12
JournalEuropean Journal of Immunology
Volume43
Issue number8
DOIs
Publication statusPublished - Aug 2013

Keywords

  • Conversion
  • Human
  • Regulatory T (Treg) cells
  • STAT3
  • Th17
  • HYPER-IGE SYNDROME
  • RHEUMATOID-ARTHRITIS
  • TH17 CELLS
  • AUTOIMMUNE-DISEASE
  • SYNOVIAL-FLUID
  • IN-VITRO
  • DIFFERENTIATION
  • TRANSPLANTATION
  • INFLAMMATION
  • SUPPRESSION

Fingerprint

Dive into the research topics of 'CD161 expression characterizes a sub-population of human regulatory T cells that produces IL-17 in a STAT3 dependent manner'. Together they form a unique fingerprint.

Cite this