Introduction Herein, we developed an engineered extracellular vehicle (EV)-based method for ameliorating inflammatory responses in psoriasis. Methods EVs, derived from annexin A1 (ANXA1) overexpressing T cells, were co-extruded with M2 macrophage membrane to obtain engineered EVs. In vitro, the effect of engineered EVs on macrophage polarization was evaluated by real-time PCR. In imiquimod (IMQ)-induced psoriasis-like mouse model, the efficacy of engineered EVs in ameliorating psoriatic inflammation was evaluated by Psoriasis Area and Severity Index (PASI) score and immunohistochemistry staining after subcutaneous injection of EVs. Results The engineered EVs not only preserved the high stability of M2 macrophage membrane but also retained the macrophage reprogramming potential of ANXA1 overexpressed in T cells. In the psoriasis-like mouse model, subcutaneous injection of engineered EVs successfully reduced the PASI score and the levels of pro-inflammatory cytokines, including IL-1 beta, IL-6, and TNF-alpha. Along with high biosafety, the administration of EVs also rescued the histomorphological changes of spleen, liver, and kidney. Conclusions The engineered EVs exhibited the potential to alleviate inflammation of psoriasis, providing new insights and potential strategies for the immunotherapies of psoriasis.
基金：
This work was supported by the National Key R&D Program of China [2019YFA09006100]; the National Natural Science Foundation of China Grants [81830051, 31961133011, and 32130041]; Shanghai Academic Research Leader [16XD1403800]; and the Innovative Research Team of High-Level Local Universities in Shanghai; and Shanghai Collaborative Innovation Center of Cellular Homeostasis Regulation and Human Diseases.
第一作者机构：[1]Shanghai Jiao Tong Univ, Ruijin Hosp, Shanghai Inst Immunol, Ctr Immune Related Dis,Sch Med, Shanghai 200025, Peoples R China
共同第一作者：
通讯作者：
通讯机构：[1]Shanghai Jiao Tong Univ, Ruijin Hosp, Shanghai Inst Immunol, Ctr Immune Related Dis,Sch Med, Shanghai 200025, Peoples R China[8]Tongji Univ, Shanghai Skin Dis Hosp, Sch Med, Dept Integrated TCM & Western Med, Shanghai, Peoples R China
推荐引用方式(GB/T 7714)：
Wang Zeng,Qin Zhizhen,Wang Jiadie,et al.Engineering extracellular vesicles with macrophage membrane fusion for ameliorating imiquimod-induced psoriatic skin inflammation[J].JOURNAL OF DERMATOLOGICAL TREATMENT.2023,34(1):doi:10.1080/09546634.2023.2220445.
APA：
Wang, Zeng,Qin, Zhizhen,Wang, Jiadie,Xu, Xinqi,Zhang, Mengxin...&Li, Bin.(2023).Engineering extracellular vesicles with macrophage membrane fusion for ameliorating imiquimod-induced psoriatic skin inflammation.JOURNAL OF DERMATOLOGICAL TREATMENT,34,(1)
MLA：
Wang, Zeng,et al."Engineering extracellular vesicles with macrophage membrane fusion for ameliorating imiquimod-induced psoriatic skin inflammation".JOURNAL OF DERMATOLOGICAL TREATMENT 34..1(2023)
