title: Deletion of microRNA-155 reduces autoantibody responses and alleviates lupus-like disease in the Fas(lpr) mouse.
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.
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115.
authors.forename: To-Ha
authors.initials: TH
authors.lastname: Thai
authors.forename: Heide Christine
authors.initials: HC
authors.lastname: Patterson
authors.forename: Duc-Hung
authors.initials: DH
authors.lastname: Pham
authors.forename: Katalin
authors.initials: K
authors.lastname: Kis-Toth
authors.forename: Denise A
authors.initials: DA
authors.lastname: Kaminski
authors.forename: George C
authors.initials: GC
authors.lastname: Tsokos
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis / Q000276:immunology*; D015152:Blotting, Northern; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D017353:Gene Deletion; D006652:Histological Techniques; D007150:Immunohistochemistry; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics* / Q000276:immunology*; D016482:Urinalysis
chemical_list: D001323:Autoantibodies; C524942:MIRN155 microRNA, human; D035683:MicroRNAs
keywords: ERK pathways; SHIP-1