2017/02/25 by SunAh Kang, Yuri Fedoriw, Ethan Brenneman +3 · 2 citations
Medicine · Immunology and Microbiology · #Systemic Lupus Erythematosus Research #T-cell and B-cell Immunology #Renal Diseases and Glomerulopathies
paper · pdf · doi:10.4049/jimmunol.1600281
openalex publication_date 2017/02/25 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/30
Abstract Tissue-specific immune responses play an important role in the pathology of autoimmune diseases. In systemic lupus erythematosus, deposits of IgG-immune complexes and the activation of complement in the kidney have long been thought to promote inflammation and lupus nephritis. However, the events that localize cells in non-lymphoid tertiary organs and sustain tissue-specific immune responses remain undefined. In this manuscript, we show that BAFF promotes events leading to lupus nephritis. Using an inducible model of systemic lupus erythematosus, we found that passive transfer of antinucleosome IgG into AID−/−MRL/lpr mice elevated autoantibody levels and promoted lupus nephritis by inducing BAFF production in the kidneys, and the formation of renal tertiary lymphoid structures (TLSs). Reducing BAFF in vivo prevented the formation of TLSs and lupus nephritis; however, it did not reduce immune cell infiltrates, or the deposits of IgG and complement in the kidney. Mechanistically, lowering BAFF levels also diminished the number of T cells positioned inside the glomeruli and reduced inflammation. Thus, BAFF plays a previously unappreciated role in lupus nephritis by inducing renal TLSs and regulating the position of T cells within the glomeruli.