State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou, 310003, China.
National Clinical Research Center for Infectious Diseases, 79 Qingchun Rd., Hangzhou, 310003, China.
Stem Cell Res Ther. 2023 Aug 8;14(1):197. doi: 10.1186/s13287-023-03438-w.
Mesenchymal stem cell (MSC) treatment plays a major role in the management of acute lung injury (ALI), and neutrophils are the initial line of defense against ALI. However, the effect of MSCs on neutrophils in ALI remains mostly unknown.
We investigated the characteristics of neutrophils in lung tissue of ALI mice induced by lipopolysaccharide after treatment with MSCs using single-cell RNA sequencing. Neutrophils separated from lung tissue in ALI were co-cultured with MSCs, and then samples were collected for reverse transcription-polymerase chain reaction and flow cytometry.
During inflammation, six clusters of neutrophils were identified, annotated as activated, aged, and circulatory neutrophils. Activated neutrophils had higher chemotaxis, reactive oxygen species (ROS) production, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase scores than aged neutrophils. Circulatory neutrophils occurred mainly in healthy tissue and were characterized by higher expression of Cxcr2 and Sell. Activated neutrophils tended to exhibit higher expression of Cxcl10 and Cd47, and lower expression of Cd24a, while aged neutrophils expressed a lower level of Cd47 and higher level of Cd24a. MSC treatment shifted activated neutrophils toward an aged neutrophil phenotype by upregulating the expression of CD24, thereby inhibiting inflammation by reducing chemotaxis, ROS production, and NADPH oxidase.
We identified the immunosuppressive effects of MSCs on the subtype distribution of neutrophils and provided new insight into the therapeutic mechanism of MSC treatment in ALI.
间充质干细胞（MSC）治疗在急性肺损伤（ALI）的治疗中起着重要作用，而中性粒细胞是 ALI 的第一道防线。然而，间充质干细胞对 ALI 中性粒细胞的影响在很大程度上尚不清楚。
我们使用单细胞 RNA 测序研究了脂多糖诱导的 ALI 小鼠肺组织中 MSC 治疗后中性粒细胞的特征。将 ALI 肺组织中分离出的中性粒细胞与 MSC 共培养，然后收集样本进行逆转录-聚合酶链反应和流式细胞术。
在炎症过程中，鉴定出了六个中性粒细胞簇，被注释为活化、衰老和循环中性粒细胞。活化的中性粒细胞具有更高的趋化性、活性氧（ROS）产生和烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶评分，高于衰老的中性粒细胞。循环中性粒细胞主要发生在健康组织中，其特征是 Cxcr2 和 Sell 的表达更高。活化的中性粒细胞倾向于表现出更高的 Cxcl10 和 Cd47 表达，以及更低的 Cd24a 表达，而衰老的中性粒细胞表达更低的 Cd47 和更高的 Cd24a 表达。MSC 治疗通过上调 CD24 的表达，使活化的中性粒细胞向衰老的中性粒细胞表型转变，从而通过减少趋化性、ROS 产生和 NADPH 氧化酶来抑制炎症。
我们确定了 MSC 对中性粒细胞亚群分布的免疫抑制作用，并为 MSC 治疗 ALI 的治疗机制提供了新的见解。
