Silencing miR-146a influences B cells and ameliorates experimental autoimmune myasthenia gravis.

Abstract

MicroRNAs have been shown to be important regulators of immune homeostasis as patients with aberrant microRNA expression appeared to be more susceptible to autoimmune diseases. We recently found that miR-146a was up-regulated in activated B cells in response to rat acetylcholine receptor (AChR) α-subunit 97-116 peptide, and this up-regulation was significantly attenuated by AntagomiR-146a. Our data also demonstrated that silencing miR-146a with its inhibitor AntagomiR-146a effectively ameliorated clinical myasthenic symptoms in mice with ongoing experimental autoimmune myasthenia gravis. Furthermore, multiple defects were observed after miR-146a was knocked down in B cells, including decreased anti-R97-116 antibody production and class switching, reduced numbers of plasma cells, memory B cells and B-1 cells, and weakened activation of B cells. Previously, miR-146a has been identified as a nuclear factor-κB-dependent gene and predicted to base pair with the tumour necrosis factor receptor-associated factor 6 (TRAF6) and interleukin-1 receptor-associated kinase 1 (IRAK1) genes to regulate the immune response. However, our study proved that miR-146a inhibition had no effect on the expression of TRAF6 and IRAK1 in B cells. This result suggests that the function of miR-146a in B cells does not involve these two target molecules. We conclude that silencing miR-146a exerts its therapeutic effects by influencing the B-cell functions that contribute to the autoimmune pathogenesis of myasthenia gravis.

• Authors: JunMei Zhang, Ge Jia, Qun Liu, Jue Hu, Mei Yan, BaiFeng Yang, Huan Yang, WenBin Zhou, Jing Li
• Journal: Immunology (Immunology) Vol. 144 Issue 1 Pg. 56-67 (Jan 2015) ISSN: 1365-2567 [Electronic] England
• PMID: 24962817 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 John Wiley & Sons Ltd.

Chemical References

• MicroRNAs
• Mirn146 microRNA, mouse
• TNF Receptor-Associated Factor 6
• Interleukin-1 Receptor-Associated Kinases
• Irak1 protein, mouse

Topics

• Animals
• B-Lymphocytes (immunology, pathology)
• Female
• Gene Expression Regulation (genetics, immunology)
• Gene Knockdown Techniques
• Gene Silencing
• Interleukin-1 Receptor-Associated Kinases (genetics, immunology)
• Mice
• MicroRNAs (genetics, immunology)
• Myasthenia Gravis, Autoimmune, Experimental (genetics, immunology, pathology, therapy)
• Rats
• TNF Receptor-Associated Factor 6 (genetics, immunology)