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Sci Rep. 2017 Aug 11;7(1):7969. doi: 10.1038/s41598-017-08516-7.

Basophils contribute to pristane-induced Lupus-like nephritis model.

Author information

1
Centre de Recherche sur l'Inflammation, INSERM UMR1149, CNRS ERL8252, Université Paris Diderot, Sorbonne Paris Cité, Faculté de Médecine site Bichat, Laboratoire d'Excellence Inflamex, DHU FIRE, Paris, France.
2
Department of Immune Regulation, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, 113-8510, Japan.
3
Department of Internal Medicine, Faculté de Médecine site Bichat, DHU FIRE, Paris, France.
4
Department of Nephrology, Hôpital Bichat, Assistance Publique-Hôpitaux de Paris, Université Paris Diderot, Faculté de Médecine site Bichat, DHU FIRE, Paris, France.
5
Centre de Recherche sur l'Inflammation, INSERM UMR1149, CNRS ERL8252, Université Paris Diderot, Sorbonne Paris Cité, Faculté de Médecine site Bichat, Laboratoire d'Excellence Inflamex, DHU FIRE, Paris, France. nicolas.charles@inserm.fr.

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.

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