Format

Send to

Choose Destination
See comment in PubMed Commons below
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.

Author information

1
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, USA.
2
Department of Genetics, Yale Stem Cell Center, Yale Cancer Center, and Yale Center for RNA Science and Medicine, Yale University, New Haven, Connecticut, USA.
3
Department of Immunology and Oncology, National Biotechnology Center, Madrid, Spain.

Abstract

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.

PMID:
26901150
PMCID:
PMC4803625
DOI:
10.1038/ni.3385
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group Icon for PubMed Central
    Loading ...
    Support Center