Role of myeloid regulatory cells (MRCs) in maintaining tissue homeostasis and promoting tolerance in autoimmunity, inflammatory disease and transplantation

Cancer Immunol Immunother. 2019 Apr;68(4):661-672. doi: 10.1007/s00262-018-2264-3. Epub 2018 Oct 24.

Abstract

Myeloid cells play a pivotal role in regulating innate and adaptive immune responses. In inflammation, autoimmunity, and after transplantation, myeloid cells have contrasting roles: on the one hand they initiate the immune response, promoting activation and expansion of effector T-cells, and on the other, they counter-regulate inflammation, maintain tissue homeostasis, and promote tolerance. The latter activities are mediated by several myeloid cells including polymorphonuclear neutrophils, macrophages, myeloid-derived suppressor cells, and dendritic cells. Since these cells have been associated with immune suppression and tolerance, they will be further referred to as myeloid regulatory cells (MRCs). In recent years, MRCs have emerged as a therapeutic target or have been regarded as a potential cellular therapeutic product for tolerance induction. However, several open questions must be addressed to enable the therapeutic application of MRCs including: how do they function at the site of inflammation, how to best target these cells to modulate their activities, and how to isolate or to generate pure populations for adoptive cell therapies. In this review, we will give an overview of the current knowledge on MRCs in inflammation, autoimmunity, and transplantation. We will discuss current strategies to target MRCs and to exploit their tolerogenic potential as a cell-based therapy.

Keywords: Dendritic cells; Monocytes/macrophages; Mye-EUNITER; Myeloid regulatory cells (MRCs); Polymorphonuclear neutrophils; Tolerance.

Publication types

  • Review

MeSH terms

  • Animals
  • Autoimmunity*
  • Biomarkers
  • Disease Susceptibility
  • Homeostasis*
  • Humans
  • Immune Tolerance*
  • Immunomodulation
  • Immunophenotyping
  • Inflammation / etiology*
  • Inflammation / metabolism*
  • Macrophages / immunology
  • Macrophages / metabolism
  • Monocytes / immunology
  • Monocytes / metabolism
  • Myeloid Cells / immunology*
  • Myeloid Cells / metabolism*
  • Neutrophils / immunology
  • Neutrophils / metabolism
  • Organ Transplantation
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Transplantation, Homologous

Substances

  • Biomarkers