Arthritis Program, Toronto Western Hospital, University Health Network, 399 Bathurst Street, Toronto, Ontario, M5T 2S8, Canada.
Division of Genetics and Development, Krembil Research Institute, University Health Network, 60 Leonard Avenue, Toronto, Ontario, M5T 2R1, Canada.
Nat Rev Rheumatol. 2016 Sep;12(9):517-31. doi: 10.1038/nrrheum.2016.92. Epub 2016 Jun 23.
Autophagy, an endogenous process necessary for the turnover of organelles, maintains cellular homeostasis and directs cell fate. Alterations to the regulation of autophagy contribute to the progression of various rheumatic diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), osteoarthritis (OA) and systemic sclerosis (SSc). Implicit in the progression of these diseases are cell-type-specific responses to surrounding factors that alter autophagy: chondrocytes within articular cartilage show decreased autophagy in OA, leading to rapid cell death and cartilage degeneration; fibroblasts from patients with SSc have restricted autophagy, similar to that seen in aged dermal fibroblasts; fibroblast-like synoviocytes from RA joints show altered autophagy, which contributes to synovial hyperplasia; and dysregulation of autophagy in haematopoietic lineage cells alters their function and maturation in SLE. Various upstream mechanisms also contribute to these diseases by regulating autophagy as part of their signalling cascades. In this Review, we discuss the links between autophagy, immune responses, fibrosis and cellular fates as they relate to pathologies associated with rheumatic diseases. Therapies in clinical use, and in preclinical or clinical development, are also discussed in relation to their effects on autophagy in rheumatic diseases.
自噬是一种维持细胞内环境稳定和决定细胞命运的必要的细胞器内源性过程。自噬调控的改变有助于各种风湿性疾病的进展，包括系统性红斑狼疮（SLE）、类风湿关节炎（RA）、骨关节炎（OA）和系统性硬皮病（SSc）。这些疾病的进展中包含着对周围改变自噬的因素的特定细胞类型反应：关节软骨中的软骨细胞在 OA 中表现出自噬减少，导致细胞快速死亡和软骨退化；SSc 患者的成纤维细胞自噬受到限制，类似于老年真皮成纤维细胞；RA 关节中的成纤维细胞样滑膜细胞表现出自噬改变，这有助于滑膜增生；SLE 中造血谱系细胞的自噬失调改变了它们的功能和成熟。各种上游机制也通过调节自噬作为其信号级联的一部分，参与这些疾病。在这篇综述中，我们讨论了自噬、免疫反应、纤维化和细胞命运之间的联系，以及它们与风湿性疾病相关的病理学之间的关系。还讨论了临床应用、临床前或临床开发中的治疗方法，以及它们对风湿性疾病自噬的影响。
