Toll-like receptor 9 antagonist suppresses humoral immunity in experimental autoimmune myasthenia gravis. (February 2018)

• Record Type: Journal Article
• Authors: Zhang, Peng; Yang, Chun-lin; Liu, Ru-tao; Li, Heng; Zhang, Min; Zhang, Na; Yue, Long-tao; Wang, Cong-cong; Dou, Ying-chun; Duan, Rui-sheng
• Is Part Of: Molecular immunology. Volume 94(2018:Feb.)
• Page Start: 200
• Page End: 208
• Publication Date: 2018-02
• Subjects: TLR9 toll-like receptor 9 -- ODN oligodeoxynucleotide -- DCs dendritic cells -- Tfh follicular helper T cells -- GC germinal centre -- MG myasthenia gravis -- AchR acetylcholine receptor -- NMJ neuromuscular junction -- PAMPs pathogen-associated molecular patterns -- pDCs plasmacytoid dendritic cells -- MS multiple sclerosis -- SLE systemic lupus erythematosus -- APCs antigen-presenting cells; Toll-like receptor 9 -- Experimental autoimmune myasthenia gravis -- Follicular helper T cells -- Germinal centre; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2018.01.005
• Languages: English
• ISSNs: 0161-5890

Abstract

Graphical abstract: Highlights: Ablation of TLR9 signalling alleviates EAMG clinical symptoms through disrupting humoral immunity. H154 modulates antibody levels via Tfh and germinal center B cells. Suppressive ODNs of TLR9 pathway regulates B cell function by decreasing the level of TLR9 expression. Potential pharmacological strategy for myasthenia gravis. Abstract: Recent studies have demonstrated the important role of toll-like receptor 9 (TLR9) signalling in autoimmune diseases, but its role in myasthenia gravis (MG) has not been fully established. We show herein that blocking TLR9 signalling via the suppressive oligodeoxynucleotide (ODN) H154 alleviated the symptoms of experimental autoimmune myasthenia gravis (EAMG). With the downregulation of dendritic cells (DCs), TLR9 interruption reduced follicular helper T cells (Tfh) and germinal centre (GC) B cells, leading to decreased antibody production. In addition, TLR9 + B cells as well as total B cells in the spleen were inhibited by H154. These findings highlight the critical role of TLR9 in EAMG and suggest that the inhibition of the TLR9 pathway might be a potential pharmacological strategy for the treatment of myasthenia gravis.