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Clinical Reviews in Allergy & Immunology
Published in: Clinical Reviews in Allergy & Immunology 1/2017

01-02-2017

Review on Toll-Like Receptor Activation in Myasthenia Gravis: Application to the Development of New Experimental Models

Authors: Marieke Robinet, Solène Maillard, Mélanie A. Cron, Sonia Berrih-Aknin, Rozen Le Panse

Published in: Clinical Reviews in Allergy & Immunology | Issue 1/2017

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Abstract

Abnormal toll-like receptor (TLR) activation and uncontrolled resolution of inflammation are suspected to play a key role in the development of autoimmune diseases. Acquired myasthenia gravis (MG) is an invalidating neuromuscular disease leading to muscle weaknesses. MG is mainly mediated by anti-acetylcholine receptor (AChR) autoantibodies, and thymic hyperplasia characterized by ectopic germinal centers is a common feature in MG. An abnormal expression of certain TLRs is observed in the thymus of MG patients associated with the overexpression of interferon (IFN)-β, the orchestrator of thymic changes in MG. Experimental models have been developed for numerous autoimmune diseases. These models are induced by animal immunization with a purified antigen solubilized in complete Freund’s adjuvant (CFA) containing heat-inactivated mycobacterium tuberculosis (MTB). Sensitization against the antigen is mainly due to the activation of TLR signaling pathways by the pathogen motifs displayed by MTB, and attempts have been made to substitute the use of CFA by TLR agonists. AChR emulsified in CFA is used to induce the classical experimental autoimmune MG model (EAMG). However, the TLR4 activator lipopolysaccharide (LPS) has proved to be efficient to replace MTB and induce a sensitization against purified AChR. Poly(I:C), the well-known TLR3 agonist, is also able by itself to induce MG symptoms in mice associated with early thymic changes as observed in human MG. In this review, we discuss the abnormal expression of TLRs in MG patients and we describe the use of TLR agonists to induce EAMG in comparison with other autoimmune experimental models.
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Metadata
Title
Review on Toll-Like Receptor Activation in Myasthenia Gravis: Application to the Development of New Experimental Models
Authors
Marieke Robinet
Solène Maillard
Mélanie A. Cron
Sonia Berrih-Aknin
Rozen Le Panse
Publication date
01-02-2017
Publisher
Springer US
Published in
Clinical Reviews in Allergy & Immunology / Issue 1/2017
Print ISSN: 1080-0549
Electronic ISSN: 1559-0267
DOI
https://doi.org/10.1007/s12016-016-8549-4

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