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 language | English (US) |
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Pages (from-to) | 2643-2651 |
Number of pages | 9 |
Journal | Journal of Immunology |
Volume | 208 |
Issue number | 12 |
DOIs | |
State | Published - Jun 15 2022 |
Bibliographical note
Publisher Copyright:© 2022 by TheAmericanAssociation of Immunologists, Inc.