4.8 Article

Regulation of T-independent B-cell responses by microRNA-146a

Journal

FRONTIERS IN IMMUNOLOGY
Volume 13, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2022.984302

Keywords

B-cell; microRNA; extrafollicular B cell response; Traf6; NFkB

Categories

Funding

  1. NIH National Institute of Arthritis and Musculoskeletal and Skin Diseases [K08AR072787]
  2. NIH National Cancer Institute [R01CA166540, R01CA264986]
  3. NIH NIAID [R21AI132869]
  4. NIH [AI-28697, P30CA016042]
  5. David Geffen School of Medicine at UCLA
  6. JCCC
  7. UCLA AIDS Institute

Ask authors/readers for more resources

The microRNA miR-146a is a negative regulator of the immune transcription factor NFκB and plays important roles in the immune system. Its deficiency leads to chronic inflammation and autoimmune disease. This study found that miR-146a suppresses B-cell responses and identified TRAF6 as a target gene. TRAF6 was shown to be required for proliferation in these B-cell responses.
The microRNA, miR-146a, is a negative feedback regulator of the central immune transcription factor, nuclear factor kappa B (NFkB). MiR-146a plays important roles in the immune system, and miR-146a deficient mice show a complex phenotype with features of chronic inflammation and autoimmune disease. In this study, we examined the role of miR-146a in extrafollicular B-cell responses, finding that miR-146a suppresses cellular responses in vivo and in vitro. Gene expression profiling revealed that miR-146a-deficient B-cells showed upregulation of interferon pathway genes, including Traf6, a known miR-146a target. We next interrogated the role of TRAF6 in these B-cell responses, finding that TRAF6 is required for proliferation by genetic and pharmacologic inhibition. Together, our findings demonstrate a novel role for miR-146a and TRAF6 in the extrafollicular B-cell responses, which have recently been tied to autoimmune disease pathogenesis. Our work highlights the pathogenetic role of miR-146a and the potential of pharmacologic inhibition of TRAF6 in autoimmune diseases in which miR-146a is deregulated.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.8
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available