Basophils contribute to pristane-induced Lupus-like nephritis model

• Published in: Scientific reports Vol. 7; no. 1; pp. 7969 - 9
• Main Authors: Dema, Barbara, Lamri, Yasmine, Pellefigues, Christophe, Pacreau, Emeline, Saidoune, Fanny, Bidault, Caroline, Karasuyama, Hajime, Sacré, Karim, Daugas, Eric, Charles, Nicolas
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 11.08.2017; Nature Publishing Group; Nature Portfolio
• Subjects: 13/21; 13/31; 14/63; 631/250/2504; 631/250/38; 64/60; 692/420; 82/1; Animals; Antigens; Autoantibodies; Autoantibodies - immunology; Autoimmune diseases; Basophils - immunology; Female; Humanities and Social Sciences; Immunology; Immunosuppressive Agents - toxicity; Inflammation; Leukocyte migration; Leukocytes (basophilic); Life Sciences; Lupus; Lupus nephritis; Lupus Nephritis - etiology; Lupus Nephritis - immunology; Lymphocytes B; Lymphocytes T; Mice; Mice, Inbred C57BL; Molecular modelling; multidisciplinary; Nephritis; Pristane; Renal failure; Rodents; Science; Science (multidisciplinary); Spleen; Systemic lupus erythematosus; Terpenes - toxicity
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-08516-7

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.