Protein Tyrosine Phosphatase PTPRS Is an Inhibitory Receptor on Human and Murine Plasmacytoid Dendritic Cells

Immunity. 2015 Aug 18;43(2):277-88. doi: 10.1016/j.immuni.2015.07.009. Epub 2015 Jul 28.

Abstract

Plasmacytoid dendritic cells (pDCs) are primary producers of type I interferon (IFN) in response to viruses. The IFN-producing capacity of pDCs is regulated by specific inhibitory receptors, yet none of the known receptors are conserved in evolution. We report that within the human immune system, receptor protein tyrosine phosphatase sigma (PTPRS) is expressed specifically on pDCs. Surface PTPRS was rapidly downregulated after pDC activation, and only PTPRS(-) pDCs produced IFN-α. Antibody-mediated PTPRS crosslinking inhibited pDC activation, whereas PTPRS knockdown enhanced IFN response in a pDC cell line. Similarly, murine Ptprs and the homologous receptor phosphatase Ptprf were specifically co-expressed in murine pDCs. Haplodeficiency or DC-specific deletion of Ptprs on Ptprf-deficient background were associated with enhanced IFN response of pDCs, leukocyte infiltration in the intestine and mild colitis. Thus, PTPRS represents an evolutionarily conserved pDC-specific inhibitory receptor, and is required to prevent spontaneous IFN production and immune-mediated intestinal inflammation.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Movement / genetics
  • Cells, Cultured
  • Colitis / genetics
  • Colitis / immunology*
  • Dendritic Cells / immunology*
  • Disease Models, Animal
  • Humans
  • Interferon-gamma / metabolism
  • Intestines / immunology*
  • Leukocytes / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptor-Like Protein Tyrosine Phosphatases, Class 2 / genetics
  • Receptor-Like Protein Tyrosine Phosphatases, Class 2 / metabolism*

Substances

  • Interferon-gamma
  • PTPRS protein, human
  • Ptprf protein, mouse
  • Ptprs protein, mouse
  • Receptor-Like Protein Tyrosine Phosphatases, Class 2