An imbalance between regulatory T cells and T helper 17 cells in acetylcholine receptor-positive myasthenia gravis patients

Abstract

A chronic autoimmune disease, myasthenia gravis (MG) is characterized in 85% of patients by antibodies directed against the acetylcholine receptor (AChR) located at the neuromuscular junction. The functional and effective balance between regulatory T cells (T_reg cells) and effector T cells (T_eff cells) is lost in the hyperplastic thymus of MG patients with antibodies specific for the AChR (AChR⁺ MG patients). The objective of this review is to describe how T_reg cells and inflammatory T cells participate in this imbalance and contribute to induce a chronic inflammatory state in the MG thymus. We discuss the origins and characteristics of T_reg cells and their reported dysfunctions in AChR⁺ MG patients. We also review the inflammatory condition observed in MG thymus, including overexpression of interleukin (IL)-1β, IL-6, and IL-23, cytokines that promote the differentiation of T helper 17 (T_H 17) cells and the expression of IL-17. We summarize the preclinical models used to determine the implication of expression of cytokines, such as IL-6, IL-12 (IL-23 subunit), IL-17, and interferon γ to the development of experimental autoimmune MG. Finally, we suggest that biological agents, such as humanized monoclonal antibodies that target the IL-23/T_H 17 pathway, should be investigated in the context of MG, as they have proven efficiency in other autoimmune diseases.

Keywords: T regulatory cells; TH17 cells; autoimmune diseases; biological therapies; interleukin 17; interleukin 23.