Endogenous erythropoietin has immunoregulatory functions that limit the expression of autoimmune kidney disease in mice

Sofia Bin, Chiara Cantarelli, Julian K. Horwitz, Micaela Gentile, Manuel Alfredo Podestà, Gaetano La Manna, Peter S. Heeger, Paolo Cravedi

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Background: Administration of recombinant erythropoietin (EPO), a kidney-produced hormone with erythropoietic functions, has been shown to have multiple immunoregulatory effects in mice and humans, but whether physiological levels of EPO regulate immune function in vivo has not been previously evaluated. Methods: We generated mice in which we could downregulate EPO production using a doxycycline (DOX)-inducible, EPO-specific silencing RNA (shEPOrtTAPOS), and we crossed them with B6.MRL-Faslpr/J mice that develop spontaneous lupus. We treated these B6.MRL/lpr shEPOrtTAPOS with DOX and serially measured anti-dsDNA antibodies, analyzed immune subsets by flow cytometry, and evaluated clinical signs of disease activity over 6 months of age in B6.MRL/lpr shEPOrtTAPOS and in congenic shEPOrtTANEG controls. Results: In B6.MRL/lpr mice, Epo downregulation augmented anti-dsDNA autoantibody levels and increased disease severity and percentages of germinal center B cells compared with controls. It also increased intracellular levels of IL-6 and MCP-1 in macrophages. Discussion: Our data in a murine model of lupus document that endogenous EPO reduces T- and B-cell activation and autoantibody production, supporting the conclusion that EPO physiologically acts as a counterregulatory mechanism to control immune homeostasis.

Original languageEnglish
Article number1195662
JournalFrontiers in Immunology
Volume14
DOIs
StatePublished - 2023

Keywords

  • TFH
  • TfR
  • erythropoietin
  • germinal center B cell
  • systemic lupus erythematosus

Fingerprint

Dive into the research topics of 'Endogenous erythropoietin has immunoregulatory functions that limit the expression of autoimmune kidney disease in mice'. Together they form a unique fingerprint.

Cite this