期刊
JOURNAL OF IMMUNOLOGY
卷 205, 期 7, 页码 1810-+出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1901056
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- National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH) [DK093695]
- National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH [AR076242, AI150178]
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 alpha v integrin plays a critical role in regulating B cell TLR signaling to self-antigens in mice. We show that deletion of av 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 IgG2c-producing plasma cells, and activation of CD4 and CD8 T cells. Our data show that alpha v-mediated regulation of TLR signaling in B cells is critical for preventing autoimmunity and indicate that loss of av 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.
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