Deletion of microRNA-155 reduces autoantibody responses and alleviates lupus-like disease in the Fas(lpr) mouse
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 autoa...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2013-12, Vol.110 (50), p.20194 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Thai, To-Ha Patterson, Heide Christine Pham, Duc-Hung Kis-Toth, Katalin Kaminski, Denise A Tsokos, George C |
| description | 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. |
| doi_str_mv | 10.1073/pnas.1317632110 |
| format | Article |
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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. 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| ispartof | Proceedings of the National Academy of Sciences - PNAS, 2013-12, Vol.110 (50), p.20194 |
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| source | JSTOR Archive Collection A-Z Listing; MEDLINE; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Animals Autoantibodies - biosynthesis Autoantibodies - immunology Blotting, Northern Blotting, Western Enzyme-Linked Immunosorbent Assay Fluorescent Antibody Technique Gene Deletion Histological Techniques Immunohistochemistry Lupus Erythematosus, Systemic - immunology Lupus Erythematosus, Systemic - prevention & control Mice Mice, Knockout MicroRNAs - genetics MicroRNAs - immunology Urinalysis |
| title | Deletion of microRNA-155 reduces autoantibody responses and alleviates lupus-like disease in the Fas(lpr) mouse |
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