1. Regulation of T-independent B-cell responses by microRNA-146a
- Author
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Jennifer K. King, Tiffany M. Tran, May H. Paing, Yuxin Yin, Amit K. Jaiswal, Ching-Hsuan Tso, Koushik Roy, David Casero, and Dinesh S. Rao
- Subjects
TNF Receptor-Associated Factor 6 ,B-Lymphocytes ,microRNA ,Inflammatory and immune system ,Immunology ,NF-kappa B ,B-cell ,Traf6 ,extrafollicular B cell response ,Autoimmune Disease ,NFkB ,Autoimmune Diseases ,Mice ,MicroRNAs ,Medical Microbiology ,Genetics ,Immunology and Allergy ,Animals ,2.1 Biological and endogenous factors ,Interferons ,Aetiology ,Biotechnology - Abstract
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.
- Published
- 2022