B cell αv integrins regulate TLR-driven autoimmunity

Mridu Acharya, Fiona Raso, Sara Sagadiev, Emily Gilbertson, Lauren Kadavy, Quan Z. Li, Mei Yan, Lynda M. Stuart, Jessica A. Hamerman, Adam Lacy-Hulbert

Research output: Contribution to journalArticlepeer-review

Abstract

Systemic lupus erythematosus (SLE) is defined by loss of B cell tolerance, resulting in production of autoantibodies against nucleic acids and other cellular Ags. Aberrant activation of TLRs by self-derived RNA and DNA is strongly associated with SLE in patients and in mouse models, but the mechanism by which TLR signaling to self-ligands is regulated remains poorly understood. In this study, we show that αv integrin plays a critical role in regulating B cell TLR signaling to self-antigens in mice. We show that deletion of αv from B cells accelerates autoantibody production and autoimmune kidney disease in the Tlr7.1 transgenic mouse model of SLE. Increased autoimmunity was associated with specific expansion of transitional B cells, extrafollicular IgG2cproducing plasma cells, and activation of CD4 and CD8 T cells. Our data show that αv-mediated regulation of TLR signaling in B cells is critical for preventing autoimmunity and indicate that loss of αv promotes escape from tolerance. Thus, we identify a new regulatory pathway in autoimmunity and elucidate upstream signals that adjust B cell activation to prevent development of autoimmunity in a mouse model.

Original languageEnglish (US)
Pages (from-to)1810-1818
Number of pages9
JournalJournal of Immunology
Volume205
Issue number7
DOIs
StatePublished - Oct 1 2020

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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