IFN-I Mediates Lupus Nephritis From the Beginning to Renal Fibrosis

Front Immunol. 2021 Apr 20:12:676082. doi: 10.3389/fimmu.2021.676082. eCollection 2021.

Abstract

Lupus nephritis (LN) is a common complication of systemic lupus erythematosus (SLE) and a major risk factor for morbidity and mortality. The abundant cell-free nucleic (DNA/RNA) in SLE patients, especially dsDNA, is a key substance in the pathogenesis of SLE and LN. The deposition of DNA/RNA-immune complexes (DNA/RNA-ICs) in the glomerulus causes a series of inflammatory reactions that lead to resident renal cell disturbance and eventually renal fibrosis. Cell-free DNA/RNA is the most effective inducer of type I interferons (IFN-I). Resident renal cells (rather than infiltrating immune cells) are the main source of IFN-I in the kidney. IFN-I in turn damages resident renal cells. Not only are resident renal cells victims, but also participants in this immunity war. However, the mechanism for generation of IFN-I in resident renal cells and the pathological mechanism of IFN-I promoting renal fibrosis have not been fully elucidated. This paper reviews the latest epidemiology of LN and its development process, discusses the mechanism for generation of IFN-I in resident renal cells and the role of IFN-I in the pathogenesis of LN, and may open a new perspective for the treatment of LN.

Keywords: IFN-I; fibrosis; lupus nephritis; nucleic acid sensors; pathogenesis; renal resident cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antigen-Antibody Complex / metabolism
  • Autoantibodies / biosynthesis
  • Fibrosis
  • Humans
  • Interferon Type I / physiology*
  • Kidney / blood supply
  • Kidney / immunology
  • Kidney / pathology*
  • Kidney Glomerulus / pathology
  • Lupus Nephritis / etiology*

Substances

  • Antigen-Antibody Complex
  • Autoantibodies
  • Interferon Type I