Abstract
Lupus nephritis (LN), one of the most severe outcomes of systemic lupus erythematosus (SLE), is initiated by glomerular deposition of immune-complexes leading to an inflammatory response and kidney failure. Autoantibodies to nuclear antigens and autoreactive B and T cells are central in SLE pathogenesis. Immune mechanisms amplifying this autoantibody production drive flares of the disease. We previously showed that basophils were contributing to LN development in a spontaneous lupus-like mouse model (constitutive Lyn−/− mice) and in SLE subjects through their activation and migration to secondary lymphoid organs (SLOs) where they amplify autoantibody production. In order to study the basophil-specific mechanisms by which these cells contribute to LN development, we needed to validate their involvement in a genetically independent SLE-like mouse model. Pristane, when injected to non-lupus-prone mouse strains, induces a LN-like disease. In this inducible model, basophils were activated and accumulated in SLOs to promote autoantibody production. Basophil depletion by two distinct approaches dampened LN-like disease, demonstrating their contribution to the pristane-induced LN model. These results enable further studies to decipher molecular mechanisms by which basophils contribute to lupus progression.
Highlights
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Lupus nephritis (LN), one of the most severe outcomes of systemic lupus erythematosus (SLE), is initiated by glomerular deposition of immune-complexes leading to an inflammatory response and kidney failure
We previously showed that basophils were contributing to LN development in a spontaneous lupus-like mouse model and in SLE subjects through their activation and migration to secondary lymphoid organs (SLOs) where they amplify autoantibody production
Summary
HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. Pristane, when injected to non-lupus-prone mouse strains, induces a LN-like disease In this inducible model, basophils were activated and accumulated in SLOs to promote autoantibody production. Systemic Lupus Erythematosus (SLE) is a complex and heterogeneous autoimmune disease characterized by the production of antibodies against self-antigens mostly of nuclear origin such as double-stranded DNA and ribonucleoproteins (RNP). These autoantibodies form pathogenic immune-complexes (ICs) once aggregated to their autoantigens and complement factors[1]. We demonstrated that basophils were activated and accumulated in SLOs in an IgE and IL-4 dependent manner during lupus-like disease development where they were supporting CD19+CD138+ short lived plasma cells to amplify autoantibody production[6, 11]. The genetic deficiencies in the spontaneous lupus-like mouse models used
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