Bim suppresses the development of SLE by limiting myeloid inflammatory responses.

ABSTRACT: The Bcl-2 family is considered the guardian of the mitochondrial apoptotic pathway. We demonstrate that Bim acts as a molecular rheostat by controlling macrophage function not only in lymphoid organs but also in end organs, thereby preventing the break in tolerance. Mice lacking Bim in myeloid cells (LysM^CreBim^fl/fl) develop a systemic lupus erythematosus (SLE)-like disease that mirrors aged Bim^-/- mice, including loss of marginal zone macrophages, splenomegaly, lymphadenopathy, autoantibodies (including anti-DNA IgG), and a type I interferon signature. LysM^CreBim^fl/fl mice exhibit increased mortality attributed to glomerulonephritis (GN). Moreover, the toll-like receptor signaling adaptor protein TRIF (TIR-domain-containing adapter-in

SUBMITTER: Tsai F 

PROVIDER: S-EPMC5716039 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature