Bim suppresses the development of SLE by limiting myeloid inflammatory responses.
J Exp Med
; 214(12): 3753-3773, 2017 Dec 04.
Article
in En
| MEDLINE
| ID: mdl-29114065
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 (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-ß) 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Myeloid Cells
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Bcl-2-Like Protein 11
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Inflammation
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Lupus Erythematosus, Systemic
Limits:
Animals
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Humans
Language:
En
Journal:
J Exp Med
Year:
2017
Document type:
Article
Affiliation country: