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 (Treg cells) and effector T cells (Teff 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 Treg 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 Treg 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 (TH 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/TH 17 pathway, should be investigated in the context of MG, as they have proven efficiency in other autoimmune diseases.

• Authors: Jose Adolfo Villegas, Jérôme Van Wassenhove, Rozen Le Panse, Sonia Berrih-Aknin, Nadine Dragin
• Journal: Annals of the New York Academy of Sciences (Ann N Y Acad Sci) Vol. 1413 Issue 1 Pg. 154-162 (02 2018) ISSN: 1749-6632 [Electronic] United States
• PMID: 29405352 (Publication Type: Journal Article, Review)
• Copyright: © 2018 New York Academy of Sciences.

Chemical References

• Antibodies, Monoclonal
• IL17A protein, human
• IL1B protein, human
• IL23A protein, human
• IL6 protein, human
• Interleukin-17
• Interleukin-1beta
• Interleukin-23 Subunit p19
• Interleukin-6
• Receptors, Cholinergic

Topics

• Animals
• Antibodies, Monoclonal (therapeutic use)
• Humans
• Interleukin-17 (biosynthesis)
• Interleukin-1beta (biosynthesis)
• Interleukin-23 Subunit p19 (immunology)
• Interleukin-6 (biosynthesis)
• Mice
• Myasthenia Gravis (immunology)
• Neuromuscular Junction (immunology)
• Receptors, Cholinergic (immunology)
• T-Lymphocytes, Regulatory (immunology)
• Th17 Cells (immunology)
• Thymus Gland (immunology, pathology)