Toll-like receptor signalling and ectopic lymphoid development in Myasthenia Gravis

The thymus of Myasthenia gravis (MG) patients is very often abnormal and possesses all the characteristics of tertiary lymphoid organs such as neoangiogenesis processes, overexpression of inflammatory cytokines and chemokines, and infiltration of B lymphocytes leading to ectopic germinal center (GC) development.

In order to develop an experimental MG model associated with thymic GCs, the authors used Poly(I:C) in the classical experimental autoimmune MG model induced by immunizations with purified AChR emulsified in complete Freund’s adjuvant. They observed that Poly(I:C) strongly favored the development of MG as almost all mice displayed MG symptoms. Nevertheless, they did not observe any ectopic GC development. Mice were then challenged with Poly(I:C) together with other toll-like receptor (TLR) agonists known to be involved in GC development and that are overexpressed in MG thymuses. Imiquimod and CpG oligodeoxynucleotides that activate TLR7 and TLR9, respectively, did not induce thymic changes. In contrast, lipopolysaccharide that activates TLR4 potentiated Poly(I:C) effects and induced a significant expression of CXCL13 mRNA in the thymus associated with a higher recruitment of B cells that induced over time thymic B-lymphoid structures.

Altogether, these data suggest that tertiary lymphoid genesis in MG thymus could result from a combined activation of TLR signaling pathways.

 

Robinet M, Villeret B, Maillard S, et al. Use of Toll-Like Receptor Agonists to Induce Ectopic Lymphoid Structures in Myasthenia Gravis Mouse Models. Front Immunol. 2017 Aug 25;8:1029.