DC Activated via dectin-1 Convert Treg Into IL-17 Producers

Eur J Immunol. 2008 Dec;38(12):3274-81. doi: 10.1002/eji.200838950.

Abstract

Th cells producing IL-17 play a pro-inflammatory role at mucosal surfaces. Treg at the same sites dampen inflammation and prevent immunopathology. Th cells producing IL-17 (Th17) and Treg are thought to be distinct populations defined by expression of the transcription factors ROR-gammat and Foxp3, respectively. Here, we show that mouse CD25(+)Foxp3(+) Treg can be converted into a hybrid T-cell population characterized by the expression of Foxp3 and ROR-gammat and the production of IL-17. Conversion was observed upon coculture with DC selectively activated via dectin-1, a C-type lectin receptor involved in fungal recognition, and depended on IL-23 produced by DC. Within the Foxp3(+) population, only Foxp3(+)ROR-gammat(+) T cells but not Foxp3(+)ROR-gammat(-)-T cells become Foxp3(+)IL-17(+) T cells. These results indicate that some Foxp3(+) T cells can produce IL-17 while retaining Foxp3 expression and suggest that Treg could play an unexpected pro-inflammatory role in some settings.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / immunology
  • Dendritic Cells / drug effects*
  • Dendritic Cells / immunology*
  • Forkhead Transcription Factors / immunology
  • Interleukin-17 / biosynthesis*
  • Interleukin-17 / immunology
  • Interleukin-2 Receptor alpha Subunit / immunology
  • Interleukin-23 / deficiency
  • Interleukin-23 / genetics
  • Interleukin-23 / metabolism
  • Lectins, C-Type
  • Membrane Proteins / pharmacology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nerve Tissue Proteins / pharmacology*
  • T-Lymphocytes, Regulatory / cytology
  • T-Lymphocytes, Regulatory / drug effects*
  • T-Lymphocytes, Regulatory / immunology*

Substances

  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Interleukin-17
  • Interleukin-2 Receptor alpha Subunit
  • Interleukin-23
  • Lectins, C-Type
  • Membrane Proteins
  • Nerve Tissue Proteins
  • dectin 1