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Nat Immunol. 2016 Apr;17(4):433-40. doi: 10.1038/ni.3385. Epub 2016 Feb 22.

The microRNA miR-148a functions as a critical regulator of B cell tolerance and autoimmunity.

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Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, USA.
Department of Genetics, Yale Stem Cell Center, Yale Cancer Center, and Yale Center for RNA Science and Medicine, Yale University, New Haven, Connecticut, USA.
Department of Immunology and Oncology, National Biotechnology Center, Madrid, Spain.


Autoreactive B cells have critical roles in a large diversity of autoimmune diseases, but the molecular pathways that control these cells remain poorly understood. We performed an in vivo functional screen of a lymphocyte-expressed microRNA library and identified miR-148a as a potent regulator of B cell tolerance. Elevated miR-148a expression impaired B cell tolerance by promoting the survival of immature B cells after engagement of the B cell antigen receptor by suppressing the expression of the autoimmune suppressor Gadd45α, the tumor suppressor PTEN and the pro-apoptotic protein Bim. Furthermore, increased expression of miR-148a, which occurs frequently in patients with lupus and lupus-prone mice, facilitated the development of lethal autoimmune disease in a mouse model of lupus. Our studies demonstrate a function for miR-148a as a regulator of B cell tolerance and autoimmunity.

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