Basophils contribute to pristane-induced Lupus-like nephritis model.
Barbara DemaYasmine LamriChristophe PellefiguesEmeline PacreauFanny SaidouneCaroline BidaultHajime KarasuyamaKarim SacréEric DaugasNicolas CharlesPublished in: Scientific reports (2017)
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.
Keyphrases
- systemic lupus erythematosus
- disease activity
- mouse model
- inflammatory response
- high glucose
- escherichia coli
- diabetic rats
- drug induced
- induced apoptosis
- early onset
- type diabetes
- lipopolysaccharide induced
- metabolic syndrome
- endothelial cells
- immune response
- toll like receptor
- cell cycle arrest
- endoplasmic reticulum stress
- lps induced
- skeletal muscle
- wild type
- case control