Myeloid-derived suppressor cells are proinflammatory and regulate collagen-induced arthritis through manipulating Th17 cell differentiation

Clin Immunol. 2015 Apr;157(2):175-86. doi: 10.1016/j.clim.2015.02.001. Epub 2015 Feb 11.

Abstract

Myeloid-derived suppressor cells (MDSC) and Th17 cells were found to expand in collagen-induced arthritis (CIA) significantly. Two subsets of MDSC, polymorphonuclear (PMN) and mononuclear (MO), were detected and their ratios varied during the development of CIA. The depletion of MDSC in vivo resulted in suppression of T-cell proliferation and decreased IL-17A and IL-1β production. The adoptive transfer of MDSC restored the severity of arthritis and Th17 cell differentiation. The depletion of MDSCs on day 35 resulted in arthritis amelioration without reaching a significant difference. Furthermore, MDSCs from CIA mice had higher production of IL-1β and promoted Th17 cell differentiation. The expansion of MDSCs in the peripheral blood of rheumatoid arthritis (RA) patients was in correlation with increased Th17 cells and disease activity DAS28. These results support the hypothesis that MDSC may play a significant proinflammatory role in the pathogenesis of CIA and RA by inducing Th17 development in an IL-1β-dependent manner.

Keywords: Collagen-induced arthritis; IL-1β; Myeloid-derived suppressor cells; Th17 cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Arthritis, Experimental / chemically induced
  • Arthritis, Experimental / immunology*
  • Arthritis, Rheumatoid / immunology*
  • Cell Differentiation / immunology*
  • Cells, Cultured
  • Collagen Type II / toxicity
  • Humans
  • Inflammation / immunology
  • Interleukin-17 / immunology
  • Interleukin-1beta / immunology
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / immunology*
  • Mice
  • Myeloid Cells / cytology
  • Myeloid Cells / immunology
  • Neutrophils / cytology
  • Neutrophils / immunology*
  • Th17 Cells / cytology
  • Th17 Cells / immunology*

Substances

  • Collagen Type II
  • IL1B protein, mouse
  • Il17a protein, mouse
  • Interleukin-17
  • Interleukin-1beta