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

Nature Immunology
Alicia Gonzalez-MartinChangchun Xiao

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.

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Methods Mentioned

BETA
flow cytometry
transfection
density gradient centrifugation
PCR
ELISA

Software Mentioned

mRNA
Bowtie2
Seq TopHat
Casava
Partek
Pipeline
Cutadapt
Prism

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