Work

Deletion of microRNA-155 reduces autoantibody responses and alleviates lupus-like disease in the Fas lpr mouse

Year: 2013

Type: article

Abstract: MicroRNA-155 (miR-155) regulates antibody responses and subsequent B-cell effector functions to exogenous antigens. However, the role of miR-155 in systemic autoimmunity is not known. Using the death receptor deficient (Fas(lpr)) lupus-prone mouse, we show here that ablation of miR-155 reduced autoantibody responses accompanied by a decrease in serum IgG but not IgM anti-dsDNA antibodies and a reduction of kidney inflammation. MiR-155 deletion in Fas(lpr) B cells restored the reduced SH2 domain-containing inositol 5'-phosphatase 1 to normal levels. In addition, coaggregation of the Fc γ receptor IIB with the B-cell receptor in miR-155(-/-)-Fas(lpr) B cells resulted in decreased ERK activation, proliferation, and production of switched antibodies compared with miR-155 sufficient Fas(lpr) B cells. Thus, by controlling the levels of SH2 domain-containing inositol 5'-phosphatase 1, miR-155 in part maintains an activation threshold that allows B cells to respond to antigens.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.1317632110

Authors: To-Ha Thai, Heide Christine Patterson, Duc-Hung Pham, Katalin Kis-Toth, Denise A. Kaminski, George C. Tsokos