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

Academic Article
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Overview

authors

  • Gonzalez-Martin, A.
  • Adams, B. D.
  • Lai, M.
  • Shepherd, J.
  • Salvador-Bernaldez, M.
  • Salvador, J. M.
  • Lu, J.
  • Nemazee, David
  • Xiao, Changchun

publication date

  • April 2016

journal

  • Nature Immunology  Journal

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.

subject areas

  • Animals
  • Apoptosis
  • Apoptosis Regulatory Proteins
  • Autoimmunity
  • B-Lymphocytes
  • Bone Marrow Transplantation
  • Cell Cycle Proteins
  • Cell Proliferation
  • Disease Models, Animal
  • HEK293 Cells
  • Humans
  • Immune Tolerance
  • Immunoblotting
  • Lupus Erythematosus, Systemic
  • Membrane Proteins
  • Mice
  • Mice, Inbred MRL lpr
  • MicroRNAs
  • Nuclear Proteins
  • PTEN Phosphohydrolase
  • Proto-Oncogene Proteins
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Analysis, RNA
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Identity

PubMed Central ID

  • PMC4803625

International Standard Serial Number (ISSN)

  • 1529-2908

Digital Object Identifier (DOI)

  • 10.1038/ni.3385

PubMed ID

  • 26901150
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Additional Document Info

start page

  • 433

end page

  • 440

volume

  • 17

issue

  • 4

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