Bim suppresses the development of SLE by limiting myeloid inflammatory responses

Fu Nien Tsai, Philip J. Homan, Hemant Agrawal, Alexander V. Misharin, Hiam Abdala-Valencia, G. Kenneth Haines, Salina Dominguez, Christina L. Bloomfield, Rana Saber, Anthony Chang, Chandra Mohan, Jack Hutcheson, Anne Davidson, G. R. Scott Budinger, Philippe Bouillet, Andrea Dorfleutner, Christian Stehlik, Deborah R. Winter, Carla M. Cuda, Harris Perlman

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


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 (LysMCreBimfl/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. LysMCreBimfl/fl mice exhibit increased mortality attributed to glomerulonephritis (GN). Moreover, the toll-like receptor signaling adaptor protein TRIF (TIR-domain-containing adapter-inducing interferon-β) is essential for GN, but not systemic autoimmunity in LysMCreBimfl/fl mice. Bim-deleted kidney macrophages exhibit a novel transcriptional lupus signature that is conserved within the gene expression profiles from whole kidney biopsies of patients with SLE. Collectively, these data suggest that the Bim may be a novel therapeutic target in the treatment of SLE.

Original languageEnglish
Pages (from-to)3753-3773
Number of pages21
JournalJournal of Experimental Medicine
Issue number12
StatePublished - 1 Dec 2017


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