Journal
NATURE IMMUNOLOGY
Volume 17, Issue 4, Pages 433-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/ni.3385
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Funding
- Pew Charitable Trusts
- Cancer Research Institute
- Lupus Research Institute
- US National Institutes of Health [R01 AI089854, R01 AI59714, RC4 AI092763]
- TSRI Flow Cytometry and Genomics Core Facilities
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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 Gadd45 alpha, 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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