UPMC Sorbonne Universities, Paris, France.
INSERM U974, Paris, France.
Ann N Y Acad Sci. 2018 Feb;1413(1):154-162. doi: 10.1111/nyas.13591. Epub 2018 Jan 24.
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 cells) and effector T cells (T 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 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 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 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 17 pathway, should be investigated in the context of MG, as they have proven efficiency in other autoimmune diseases.
一种慢性自身免疫性疾病，重症肌无力（MG）在 85%的患者中以针对位于神经肌肉接头的乙酰胆碱受体（AChR）的抗体为特征。在具有针对 AChR 的抗体的 MG 患者（AChR MG 患者）的增生胸腺中，调节性 T 细胞（T 细胞）和效应性 T 细胞（T 细胞）之间的功能和有效平衡丧失。本综述的目的是描述 T 细胞和炎症性 T 细胞如何参与这种失衡，并有助于诱导 MG 胸腺的慢性炎症状态。我们讨论了 T 细胞及其在 AChR MG 患者中的报道功能障碍的起源和特征。我们还回顾了在 MG 胸腺中观察到的炎症状态，包括白细胞介素（IL）-1β、IL-6 和 IL-23 的过度表达，这些细胞因子促进辅助性 T 细胞 17（T 17）细胞的分化和 IL-17 的表达。我们总结了用于确定细胞因子（如 IL-6、IL-12（IL-23 亚基）、IL-17 和干扰素 γ）表达对实验性自身免疫性 MG 发展的影响的临床前模型。最后，我们建议在 MG 背景下研究针对 IL-23/T 17 途径的生物制剂，例如人源化单克隆抗体，因为它们在其他自身免疫性疾病中已被证明有效。
