Novel Immunoregulatory Role of Perforin-Positive Dendritic Cells

Semin Immunopathol. 2017 Feb;39(2):121-133. doi: 10.1007/s00281-016-0589-6. Epub 2016 Aug 30.

Abstract

The recently described generation of a highly defined population of dendritic cells which express perforin and granzyme A (termed "perf-DCs") and their ability to selectively delete cognate CD8+ T cell has raised the possibility that these cells play a role in the maintenance of peripheral tolerance. Using bone marrow transplantation, we generated mice selectively lacking perforin expressing dendritic cells. These mice progressively gain weight and exhibit features resembling metabolic syndrome as well as an enhanced susceptibility to autoimmunity induction. Interestingly, these pathological phenotypes were reversed upon treatment with CD4/CD8 neutralizing antibodies. Thus, it appears that this rare subpopulation of dendritic cells (perf-DCs) displays a major regulatory role in adipose tissue inflammatory processes and in autoimmunity.

Keywords: Autoimmunity; Dendritic cells; Metabolic syndrome; Perforin.

Publication types

  • Review

MeSH terms

  • Animals
  • Autoimmunity
  • Cell Differentiation
  • Cytotoxicity, Immunologic
  • Dendritic Cells / classification
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism*
  • Disease Models, Animal
  • Disease Susceptibility
  • Encephalomyelitis, Autoimmune, Experimental
  • Histocompatibility Antigens / immunology
  • Histocompatibility Antigens / metabolism
  • Humans
  • Immune Tolerance
  • Immunomodulation*
  • Metabolic Syndrome / etiology
  • Metabolic Syndrome / metabolism
  • Perforin / genetics
  • Perforin / metabolism*
  • Signal Transduction
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism

Substances

  • Histocompatibility Antigens
  • Perforin