Toll-like receptor 9 antagonist suppresses humoral immunity in experimental autoimmune myasthenia gravis

Peng Zhang; Chun-Lin Yang; Ru-Tao Liu; Heng Li; Min Zhang; Na Zhang; Long-Tao Yue; Cong-Cong Wang; Ying-Chun Dou; Rui-Sheng Duan

doi:10.1016/j.molimm.2018.01.005

Toll-like receptor 9 antagonist suppresses humoral immunity in experimental autoimmune myasthenia gravis

Mol Immunol. 2018 Feb:94:200-208. doi: 10.1016/j.molimm.2018.01.005. Epub 2018 Jan 12.

Authors

Affiliations

¹ Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, PR China.
² Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, PR China.
³ College of Basic Medical Sciences, Shandong University of Traditional Chinese Medicine, Jinan 250355, PR China.
⁴ Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, PR China. Electronic address: ruisheng_duan@sdu.edu.cn.

PMID: 29331804
DOI: 10.1016/j.molimm.2018.01.005

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.

Keywords: Experimental autoimmune myasthenia gravis; Follicular helper T cells; Germinal centre; Toll-like receptor 9.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
B-Lymphocytes / drug effects
B-Lymphocytes / immunology
Cell Proliferation / drug effects
Dendritic Cells / drug effects
Dendritic Cells / immunology
Down-Regulation / drug effects
Down-Regulation / genetics
Female
Germinal Center / drug effects
Germinal Center / pathology
Immunity, Humoral / drug effects*
Immunity, Humoral / genetics
Myasthenia Gravis, Autoimmune, Experimental / drug therapy*
Myasthenia Gravis, Autoimmune, Experimental / genetics
Myasthenia Gravis, Autoimmune, Experimental / immunology*
Myasthenia Gravis, Autoimmune, Experimental / pathology
Oligodeoxyribonucleotides, Antisense / pharmacology*
Oligodeoxyribonucleotides, Antisense / therapeutic use*
Rats
Rats, Inbred Lew
Spleen / drug effects
Spleen / immunology
T-Lymphocytes, Helper-Inducer / drug effects
T-Lymphocytes, Helper-Inducer / immunology
Toll-Like Receptor 9 / antagonists & inhibitors*
Toll-Like Receptor 9 / genetics

Substances

Oligodeoxyribonucleotides, Antisense
Toll-Like Receptor 9