Basophils contribute to pristane-induced Lupus-like nephritis model

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantibodies / immunology
  • Basophils / immunology*
  • Female
  • Immunosuppressive Agents / toxicity
  • Lupus Nephritis / etiology
  • Lupus Nephritis / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Terpenes / toxicity

Substances

  • Autoantibodies
  • Immunosuppressive Agents
  • Terpenes
  • pristane