Deletion of microRNA-155 reduces autoantibody responses and alleviates lupus-like disease in the Fas(lpr) mouse
Thai, To-Ha × Patterson, Heide Christine Pham, Duc Hung Kis-Toth, Katalin Kaminski, Denise A Tsokos, George C #
National Academy of Sciences
Proceedings of the National Academy of Sciences of the United States of America vol:110 issue:50 pages:20194-9
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.