Th17 cells induce Th1-polarizing monocyte-derived dendritic cells

J Immunol. 2013 Aug 1;191(3):1175-87. doi: 10.4049/jimmunol.1203201. Epub 2013 Jun 21.

Abstract

In chronically inflamed tissues, such as those affected by autoimmune disease, activated Th cells often colocalize with monocytes. We investigate in this study how murine Th cells influence the phenotype and function of monocytes. The data demonstrate that Th1, Th2, and Th17 subsets promote the differentiation of autologous monocytes into MHC class II(+), CD11b(+), CD11c(+) DC that we call DCTh. Although all Th subsets induce the formation of DCTh, activated Th17 cells uniquely promote the formation of IL-12/IL-23-producing DCTh (DCTh17) that can polarize both naive and Th17 cells to a Th1 phenotype. In the inflamed CNS of mice with Th17-mediated experimental autoimmune encephalomyelitis, Th cells colocalize with DC, as well as monocytes, and the Th cells obtained from these lesions drive the formation of DCTh that are phenotypically indistinguishable from DCTh17 and polarize naive T cells toward a Th1 phenotype. These results suggest that DCTh17 are critical in the interplay of Th17- and Th1-mediated responses and may explain the previous finding that IL-17-secreting Th cells become IFN-γ-secreting Th1 cells in experimental autoimmune encephalomyelitis and other autoimmune disorders.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Autoimmunity / immunology*
  • CD11b Antigen / metabolism
  • CD11c Antigen / metabolism
  • Cell Differentiation
  • Cell Movement
  • Cell Polarity
  • Cells, Cultured
  • Central Nervous System / immunology
  • Dendritic Cells / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Female
  • Histocompatibility Antigens Class II / metabolism
  • Inflammation / immunology*
  • Interferon-gamma / metabolism
  • Interleukin-12 / biosynthesis
  • Interleukin-17 / metabolism
  • Interleukin-23 / biosynthesis
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Monocytes / immunology
  • Th1 Cells / immunology*
  • Th17 Cells / immunology*

Substances

  • CD11b Antigen
  • CD11c Antigen
  • Histocompatibility Antigens Class II
  • Interleukin-17
  • Interleukin-23
  • Interleukin-12
  • Interferon-gamma