Title: T cell PKCδ kinase inactivation induces lupus-like autoimmunity in mice.

Authors: Gorelik, Gabriela; Sawalha, Amr H; Patel, Dipak; Johnson, Kent; Richardson, Bruce

Published In Clin Immunol, (2015 Jun)

Abstract: Genetic and environmental factors contribute to the onset and progression of lupus. CD4+ T cells from patients with active lupus show a decreased ERK signaling pathway, which causes changes in gene expression. The defect points to its upstream regulator, PKCδ, which exhibits a deficient activity due to oxidative stress. Our aim was to investigate the effect of a defective PKCδ in the development of lupus. We generated a double transgenic C57BL6 × SJL mouse that expresses a doxycycline-induced dominant negative PKCδ (dnPKCδ) in T cells. The transgenic mice displayed decreased T cell ERK signaling, decreased DNMT1 expression and overexpression of methylation sensitive genes involved in the exaggerated immune response in the pathogenesis of lupus. The mice developed anti-dsDNA autoantibodies and glomerulonephritis with IgG deposition. The study indicates common pathogenic mechanisms with human lupus, suggesting that environmentally-mediated T cell PKCδ inactivation plays a causative role in lupus.

PubMed ID: 25829232

MeSH Terms: No MeSH terms associated with this publication