title: Delivery of an miR155 inhibitor by anti-CD20 single-chain antibody into B cells reduces the acetylcholine receptor-specific autoantibodies and ameliorates experimental autoimmune myasthenia gravis.
abstract: MicroRNA-155 (miR155) is required for antibody production after vaccination with attenuated Salmonella. miR155-deficient B cells generated reduced germinal centre responses and failed to produce high-affinity immunoglobulin (Ig)G1 antibodies. In this study, we observed up-regulation of miR155 in the peripheral blood mononuclear cells (PBMCs) of patients with myasthenia gravis (MG), and miR155 was also up-regulated in torpedo acetylcholine receptor (T-AChR)-stimulated B cells. We used an inhibitor of miR155 conjugated to anti-CD20 single-chain antibody to treat both the cultured B cells and the experimental autoimmune MG (EAMG) mice. Our results demonstrated that silencing of miR155 by its inhibitor impaired the B cell-activating factor (BAFF)-R-related signalling pathway and reduced the translocation of nuclear factor (NF)-κB into the nucleus. Additionally, AChR-specific autoantibodies were reduced, which may be related to the altered amounts of marginal zone B cells and memory B cells in the spleens of EAMG mice. Our study suggests that miR155 may be a promising target for the clinical therapy of MG.
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Y-Z
authors.initials: YZ
authors.lastname: Wang
authors.forename: F-F
authors.initials: FF
authors.lastname: Tian
authors.forename: M
authors.initials: M
authors.lastname: Yan
authors.forename: J-M
authors.initials: JM
authors.lastname: Zhang
authors.forename: Q
authors.initials: Q
authors.lastname: Liu
authors.forename: J-Y
authors.initials: JY
authors.lastname: Lu
authors.forename: W-B
authors.initials: WB
authors.lastname: Zhou
authors.forename: H
authors.initials: H
authors.lastname: Yang
authors.forename: J
authors.initials: J
authors.lastname: Li
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000235:genetics / Q000276:immunology; D000818:Animals; D018951:Antigens, CD20 / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015153:Blotting, Western; D002467:Cell Nucleus / Q000276:immunology / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000276:immunology; D055785:Gene Knockdown Techniques; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000276:immunology*; D009157:Myasthenia Gravis / Q000235:genetics / Q000276:immunology; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology*; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000276:immunology*; D019948:Receptors, Interleukin-4 / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D057127:Single-Chain Antibodies / Q000235:genetics / Q000276:immunology*; D014101:Torpedo / Q000276:immunology / Q000378:metabolism
chemical_list: D018951:Antigens, CD20; D001323:Autoantibodies; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; D016328:NF-kappa B; D011950:Receptors, Cholinergic; D019948:Receptors, Interleukin-4; D057127:Single-Chain Antibodies
keywords: RNA interference; experimental autoimmune myasthenia gravis; immunomodulation; miRNA