抗成纤维细胞活化蛋白的信使核糖核酸疫苗可改善炎性关节炎的小鼠模型。
mRNA vaccine against fibroblast activation protein ameliorates murine models of inflammatory arthritis.
作者信息
Zhang Xiaowei, Jozic Antony, Song Pingfang, Xu Qiang, Shi Xiaofei, Wang Hong, Bishop Lindsey, Struthers Hillary M, Rutledge John, Chen Shuang, Xu Fei, Hancock Meaghan H, Zhu Daocheng, Sahay Gaurav, Chu Cong-Qiu
机构信息
Division of Arthritis and Rheumatic Diseases, Oregon Health & Science University, VA Portland Health Care System, Portland, Oregon 97239, USA.
Department of Pharmaceutical Sciences, College of Pharmacy, Robertson Life Sciences Building, Oregon State University, Portland, Oregon 97201, USA.
出版信息
Rheumatol Immunol Res. 2023 Jul 22;4(2):90-97. doi: 10.2478/rir-2023-0013. eCollection 2023 Jun.
OBJECTIVE
Synovial fibroblasts in patients with rheumatoid arthritis (RA) contribute substantially to the perpetuation of synovitis and invasion to cartilage and bone, and are potential therapeutic targets. Fibroblast activation protein (FAP) is highly expressed by RA synovial fibroblasts and the expression is relatively specific. We tested whether FAP can serve as a molecular target to modulate synovial fibroblasts for therapy in experimental arthritis.
METHODS
mRNA encoding consensus FAP (cFAP) was encapsulated in lipid nanoparticles (LNP) and was injected intramuscularly as vaccine prior to induction of collagen-induced arthritis (CIA) and collagen antibody induced arthritis (CAIA) in mice. Development of CIA and CAIA was assessed clinically and by histology.
RESULTS
cFAP mRNA-LNP vaccine provoked immune response to cFAP and mouse FAP (mFAP); prevented onset of CIA in 40% of mice and significantly reduced the severity of arthritis. In CAIA, cFAP mRNA-LNP did not prevent onset of arthritis but significantly reduced the severity of arthritis.
CONCLUSION
cFAP mRNA-LNP vaccine was able to provoke immune response to mFAP and suppress inflammatory arthritis.
目的
类风湿关节炎（RA）患者的滑膜成纤维细胞在滑膜炎的持续以及对软骨和骨的侵袭中起重要作用，是潜在的治疗靶点。成纤维细胞活化蛋白（FAP）在RA滑膜成纤维细胞中高表达且表达相对特异。我们测试了FAP是否可作为分子靶点来调节滑膜成纤维细胞以用于实验性关节炎的治疗。
方法
编码共有FAP（cFAP）的mRNA被包裹在脂质纳米颗粒（LNP）中，并在诱导小鼠胶原诱导性关节炎（CIA）和胶原抗体诱导性关节炎（CAIA）之前作为疫苗进行肌肉注射。通过临床和组织学评估CIA和CAIA的发展情况。
结果
cFAP mRNA-LNP疫苗引发了对cFAP和小鼠FAP（mFAP）的免疫反应；在40%的小鼠中预防了CIA发作，并显著降低了关节炎的严重程度。在CAIA中，cFAP mRNA-LNP未能预防关节炎发作，但显著降低了关节炎的严重程度。
结论
cFAP mRNA-LNP疫苗能够引发对mFAP的免疫反应并抑制炎性关节炎。
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