Angiogenesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, United States.
Front Immunol. 2021 May 20;12:680568. doi: 10.3389/fimmu.2021.680568. eCollection 2021.
Autoimmune uveitis is a sight-threatening ocular inflammatory condition in which the retina and uveal tissues become a target of autoreactive immune cells. The CD47 is a ubiquitously expressed transmembrane protein which plays multiple roles in fundamental cellular functions including phagocytosis, proliferation, and adhesion. Signal regulatory protein alpha (SIRPα), one of the CD47 ligands, is predominantly expressed in myeloid lineage cells such as dendritic cells (DCs) or macrophages, and CD47-SIRPα signaling pathway is implicated in the development of autoimmune diseases. Our current study demonstrates how CD47 depletion is effective in the prevention of experimental autoimmune uveitis (EAU), an animal model of human autoimmune uveitis, in animals deficient of CD47 ( ). Systemic suppression of SIRPα DCs in animals deficient in CD47 resulted in the inability of autoreactive CD4 T cells to develop, which is crucial to induction of EAU. Of interest, retinal microglia, the resident immune cell of the retina, express SIRPα, however these cells were not operative in EAU suppression in response to CD47 depletion. These results identify CD47 as a significant regulator in the development of SIRPα DCs that is vital to disease induction in EAU.
自身免疫性葡萄膜炎是一种威胁视力的眼内炎症性疾病，其中视网膜和葡萄膜组织成为自身反应性免疫细胞的靶标。CD47 是一种广泛表达的跨膜蛋白，在包括吞噬作用、增殖和黏附在内的基本细胞功能中发挥多种作用。信号调节蛋白 α（SIRPα）是 CD47 的配体之一，主要表达于髓系细胞，如树突状细胞（DC）或巨噬细胞，CD47-SIRPα 信号通路参与自身免疫性疾病的发生。我们的研究表明，CD47 耗竭如何在预防实验性自身免疫性葡萄膜炎（EAU）中发挥作用，EAU 是人类自身免疫性葡萄膜炎的动物模型，在缺乏 CD47 的动物（）中，CD47 耗竭可有效预防 EAU。在缺乏 CD47 的动物中，系统性抑制 SIRPα DC 会导致自身反应性 CD4 T 细胞无法发育，这对 EAU 的诱导至关重要。有趣的是，视网膜小胶质细胞，即视网膜的固有免疫细胞，表达 SIRPα，但这些细胞在对 CD47 耗竭的反应中并未在 EAU 抑制中发挥作用。这些结果表明 CD47 是 SIRPα DC 发育的重要调节剂，对 EAU 诱导的疾病至关重要。
