title: 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: Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors: JunMei
authors: J
authors: Zhang
authors: Ge
authors: G
authors: Jia
authors: Qun
authors: Q
authors: Liu
authors: Jue
authors: J
authors: Hu
authors: Mei
authors: M
authors: Yan
authors: BaiFeng
authors: B
authors: Yang
authors: Huan
authors: H
authors: Yang
authors: WenBin
authors: W
authors: Zhou
authors: Jing
authors: J
authors: Li
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D053592:Interleukin-1 Receptor-Associated Kinases / Q000235:genetics / Q000276:immunology; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000276:immunology*; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D051381:Rats; D048029:TNF Receptor-Associated Factor 6 / Q000235:genetics / Q000276:immunology
chemical_list: D035683:MicroRNAs; C534190:Mirn146 microRNA, mouse; D048029:TNF Receptor-Associated Factor 6; D053592:Interleukin-1 Receptor-Associated Kinases; C507769:Irak1 protein, mouse
keywords: RNA interference; experimental autoimmune myasthenia gravis; interleukin-1 receptor-associated kinase-1; miR-146a; tumour necrosis factor receptor-associated factor-6