Details

Autor(en) / Beteiligte

• Tsai, FuNien
• Homan, Philip J
• Agrawal, Hemant
• Misharin, Alexander V
• Abdala-Valencia, Hiam
• Haines, 3rd, G Kenneth
• Dominguez, Salina
• Bloomfield, Christina L
• Saber, Rana
• Chang, Anthony
• Mohan, Chandra
• Hutcheson, Jack
• Davidson, Anne
• Budinger, G R Scott
• Bouillet, Philippe
• Dorfleutner, Andrea
• Stehlik, Christian
• Winter, Deborah R
• Cuda, Carla M
• Perlman, Harris

Titel

Bim suppresses the development of SLE by limiting myeloid inflammatory responses

Ist Teil von

• The Journal of experimental medicine, 2017-12, Vol.214 (12), p.3753-3773

Ort / Verlag

United States: Rockefeller University Press

Erscheinungsjahr

2017

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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 Bim ) 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 Bim 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 LysM Bim 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.