Neutrophils in Rheumatoid Arthritis: Breaking Immune Tolerance and Fueling Disease

Trends Mol Med. 2019 Mar;25(3):215-227. doi: 10.1016/j.molmed.2018.12.008. Epub 2019 Jan 29.

Abstract

Rheumatoid arthritis (RA), a common autoimmune disease, is characterized by a highly coordinated inflammatory response that involves innate and adaptive immunity. One of the hallmarks of RA is an immune response directed at citrullinated peptides that are specifically targeted by anticitrullinated protein antibodies (ACPAs). Among the various mechanisms by which neutrophils may promote immune dysregulation in RA, their ability to extrude neutrophil extracellular traps has recently been implicated in the development of ACPAs. In the synovium, neutrophils interact with resident fibroblast-like synoviocytes to endow them with antigen-presenting cell capabilities and an inflammatory phenotype. Further understanding how neutrophils modulate autoimmunity and tissue damage in RA may lead to the development of novel effective therapies.

Keywords: NETosis; low-density granulocyte; neutrophil; rheumatoid arthritis.

Publication types

  • Review

MeSH terms

  • Animals
  • Arthritis, Rheumatoid / etiology*
  • Arthritis, Rheumatoid / metabolism*
  • Arthritis, Rheumatoid / pathology
  • Autoimmunity
  • Biomarkers
  • Cytokines / metabolism
  • Disease Models, Animal
  • Disease Susceptibility
  • Extracellular Traps / immunology
  • Extracellular Traps / metabolism
  • Granulocytes / immunology
  • Granulocytes / metabolism
  • Humans
  • Immune Tolerance
  • Neutrophils / immunology*
  • Neutrophils / metabolism*

Substances

  • Biomarkers
  • Cytokines