Bim suppresses the development of SLE by limiting myeloid inflammatory responses

J Exp Med. 2017 Dec 4;214(12):3753-3773. doi: 10.1084/jem.20170479. Epub 2017 Nov 7.


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.

MeSH terms

  • Adaptor Proteins, Vesicular Transport / metabolism
  • Adoptive Transfer
  • Animals
  • Autoimmunity
  • Bcl-2-Like Protein 11 / deficiency
  • Bcl-2-Like Protein 11 / metabolism*
  • Cell Survival
  • Gene Deletion
  • Gene Expression Profiling
  • Glomerulonephritis / pathology
  • Humans
  • Inflammation / metabolism
  • Inflammation / pathology*
  • Kidney / pathology
  • Lupus Erythematosus, Systemic / metabolism*
  • Lupus Erythematosus, Systemic / pathology*
  • Macrophages / metabolism
  • Macrophages / pathology
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Myeloid Cells / metabolism*
  • Myeloid Differentiation Factor 88 / metabolism
  • Phenotype
  • Protein Binding
  • Protein Domains
  • Spleen / pathology


  • Adaptor Proteins, Vesicular Transport
  • Bcl-2-Like Protein 11
  • Myeloid Differentiation Factor 88
  • TICAM-1 protein, mouse