先天免疫系统
CD47型
免疫系统
巨噬细胞
免疫学
炎症
生物
先天性淋巴细胞
细胞生物学
癌症研究
生物化学
体外
作者
Zhanxue Xu,Xiaofan Mao,Xingyu Lu,Peilin Shi,Jingping Ye,Xin-Rui Yang,Qing‐Ling Fu,Chao He,Dandan Su,Yichu Nie,Longshan Liu,Changxi Wang,Benjie Zhou,Wei Luo,Fang Cheng,Hongbo Chen
标识
DOI:10.1002/adhm.202302443
摘要
Although immunosuppressive drugs for targeting T cells are the standard of care in acute transplantation rejection, the role of innate immune cells should not be ignored. Here, single-cell RNA sequencing (scRNA-seq) and flow cytometry are performed to reveal the dynamic changes of innate immune cells within the acute rejection time and find a significantly-increased presence of Ly6G- Ly6C+ inflammatory macrophages and decreased presence of neutrophils among all types of immune cells. Next, to further explore potential targets regulating Ly6G- Ly6C+ inflammatory macrophages, scRNA-seq is used to analyze the reciprocal signaling of both neutrophils and macrophages, along with the surface genes of macrophages. It is found that activating colony-stimulating factor 1/ colony-stimulating factor 1 receptor (CSF1/CSF1R) andcluster of differentiation 47/signal regulatory protein α (CD47/SIRPα) signaling may serve as a strategy to relieve Ly6G- Ly6C+ inflammatory macrophage-mediated early graft rejection. To investigate this hypothesis, CSF1/CD47 dual-targeting nanovesicles (NVs) derived from IFN-γ-stimulated induced pluripotent stem cell-derived mesenchymal stem cells ( iPSC-MSCs )are designed and constructed. It is confirmed that CSF1/CD47 NVs synergistically induce the differentiation of Ly6G- Ly6C- M2 inhibitory macrophages by the CSF1/CSF1R pathway, and inhibit the phagocytosis of inflammatory macrophages and inflammatory response by the CD47/SIRPα pathway, ultimately relieving immune rejection. This study highlights the power of dual-targeting CSF1/CD47 NVs as an immunosuppressant against early innate immune responses with the potential for broad clinical applications.
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