CD47 Promotes Autoimmune Valvular Carditis by Impairing Macrophage Efferocytosis and Enhancing Cytokine Production

Lee A. Meier, Jessica L. Faragher, Victoria Osinski, Jennifer L. Auger, Rochus Voeller, Aubyn Marath, Bryce A. Binstadt

Research output: Contribution to journalArticlepeer-review

Abstract

Systemic autoantibody-mediated diseases accelerate chronic cardiovascular disease in humans. In the K/B.g7 mouse model of spontaneous autoantibody-mediated inflammatory arthritis, valvular carditis arises in part because of Fc receptor-mediated activation of macrophages, leading to production of pathogenic TNF and IL-6. In this study, we explored whether impaired efferocytosis mediated by the interaction of CD47-expressing apoptotic cells with signal regulatory protein α (SIRPα) on macrophages contributes to disease progression in this model. CD47-expressing apoptotic cells and SIRPα+ macrophages were abundant in inflamed/rheumatic cardiac valves from both mice and humans. In vivo anti-CD47 blockade both prevented and treated valvular carditis in K/B.g7 mice. Blocking CD47 enhanced macrophage efferocytosis and reduced macrophage production of TNF and IL-6. These studies highlight the CD47:SIRPα interaction as a key driver of chronic cardiac valve inflammation and suggest these molecules as potential therapeutic targets to reduce cardiovascular disease risk in autoantibody-driven inflammatory diseases.

Original languageEnglish (US)
Pages (from-to)2643-2651
Number of pages9
JournalJournal of Immunology
Volume208
Issue number12
DOIs
StatePublished - Jun 15 2022

Bibliographical note

Funding Information:
This work was supported by the U.S. Department of Health and Human Services (HHS), National Institutes of Health (NIH) Grants R01-HL121093, T32-AI007313, T32-GM008244, and T32-HL144472; the Rheumatology Research Foundation (Innovative Research Grant, Medical and Graduate Student Preceptorship); a Dr.Warren & Henrietta Warwick Fellowship; the National Center

Publisher Copyright:
© 2022 by TheAmericanAssociation of Immunologists, Inc.

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

Fingerprint

Dive into the research topics of 'CD47 Promotes Autoimmune Valvular Carditis by Impairing Macrophage Efferocytosis and Enhancing Cytokine Production'. Together they form a unique fingerprint.

Cite this