Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Vienna, Austria; Department of Orthopaedic Surgery, Gunma University Graduate School of Medicine, Gunma, Japan.
Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Vienna, Austria.
J Autoimmun. 2020 Jun;110:102373. doi: 10.1016/j.jaut.2019.102373. Epub 2019 Dec 9.
The mechanistic target of rapamycin (mTOR) is a master regulator of the inflammatory response in immune and non-immune cells. In immune cells mTOR regulates metabolism to fuel cell fate decision, proliferation and effector functions. In non-immune cells, such as fibroblast, it controls inflammation-associated proliferation and migration/invasion, shapes the expression of cytokines and chemokines and promotes extracellular matrix remodeling and fibrosis. Hence, mTOR plays a critical role in chronic inflammation, where a continuous feedback between stromal cells and infiltrating immune cells result in tissue remodeling and organ damage. Activation of mTOR has been implicated in a number of chronic inflammatory diseases, especially rheumatic diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc), sjögren syndrome (SS) and seronegative spondyloarthropathy (SpA). Here we review recent advances in our understanding of the mechanism of mTOR activation in inflammation, especially in rheumatic diseases. We further discuss recent findings regarding the beneficial and side effects of mTOR inhibition in rheumatic conditions.
雷帕霉素的靶蛋白（mTOR）是免疫和非免疫细胞炎症反应的主要调节因子。在免疫细胞中，mTOR 调节代谢以促进细胞命运决定、增殖和效应功能。在非免疫细胞中，如成纤维细胞，它控制与炎症相关的增殖和迁移/侵袭，调节细胞因子和趋化因子的表达，并促进细胞外基质重塑和纤维化。因此，mTOR 在慢性炎症中起着关键作用，其中基质细胞和浸润免疫细胞之间的持续反馈导致组织重塑和器官损伤。mTOR 的激活与许多慢性炎症性疾病有关，特别是风湿性疾病，如系统性红斑狼疮（SLE）、类风湿关节炎（RA）、系统性硬化症（SSc）、干燥综合征（SS）和血清阴性脊柱关节病（SpA）。本文综述了我们对 mTOR 在炎症，特别是风湿性疾病中激活机制的理解的最新进展。我们进一步讨论了 mTOR 抑制在风湿性疾病中的有益和副作用的最新发现。
