Engineering extracellular vesicles with macrophage membrane fusion for ameliorating imiquimod-induced psoriatic skin inflammation

Abstract

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-1β, IL-6, and TNF-α. 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.

Keywords:

• Engineered extracellular vesicles
• psoriasis
• annexin A1
• macrophages

Acknowledgements

The authors thank the Shanghai Collaborative Innovation Center of Cellular Homeostasis Regulation and Human Diseases for providing constructive comments on our work and Jieqiong Chen, Le Kuai, Shouyu Ke, Xiaoxia Wang, Hao Cheng, and Qianru Huang for their valuable suggestions.

Ethical approval

The study was approved by the Ethics Committee of Shanghai Tenth People’s Hospital affiliated to Tongji University School of Medicine (Shanghai, China) and was performed in accordance with the Declaration of Helsinki.

Consent form

Informed consents were signed by all patients and donors. All animal experiments were approved by the Animal Care and Use Committee of Shanghai Jiao Tong University School of Medicine (no. A-2017-009) and were performed according to the committee-approved guidelines.

Author contributions

Zeng Wang designed the experiment and analyzed the data. Zeng Wang, Zhizhen Qin, Jiadie Wang, Xinqi Xu, Mengxin Zhang, Yuyue Liang performed the experiments. Yukun Huang conducted NTA analysis. Zengyang Yu and Yu Gong provided the human sample. Luxian Zhou provided the conception. Yiran Qiu and Minglu Ma performed the WB. The manuscript was written by Zeng Wang and Zhizhen Qin. Zhizhen Qin, Dan Li and Bin Li critically reviewed the article. All the authors read and approved the manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Data availability statement

Data will be made available on reasonable request.

Additional information

Funding

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.