单核细胞对食管和胃中巨噬细胞的更新

doi:10.3969/j.issn.1674-8115.2022.09.007

上海交通大学学报（医学版） ›› 2022, Vol. 42 ›› Issue (9): 1208-1215.doi: 10.3969/j.issn.1674-8115.2022.09.007

• 创新团队成果专栏 • 上一篇

单核细胞对食管和胃中巨噬细胞的更新

朱忆文¹^,²(), 于庆¹(), 吴欣睿¹, 路洁¹, 陈梓濠¹, GINHOUX Florent², 苏冰¹^,²(), 刘兆远¹^,²()

^1.上海交通大学医学院免疫学与微生物学系，上海 200025
^2.上海交通大学医学院上海市免疫学研究所，上海 200025

收稿日期:2022-06-13 接受日期:2022-08-29 出版日期:2022-09-28 发布日期:2022-09-28
通讯作者: 苏冰,刘兆远 E-mail:yiwen.zhu@sjtu.edu.cn;1279786056@qq.com;bingsu@sjtu.edu.cn;zhaoyuan_liu@sjtu.edu.cn
作者简介:朱忆文（1998—），女，硕士生；电子信箱：yiwen.zhu@sjtu.edu.cn
于庆（1999—）女，本科生；电子信箱：1279786056@qq.com。第一联系人：（朱忆文和于庆为本文共同第一作者）
基金资助:
国家自然科学基金(31900630);上海市青年科技启明星项目(20QA1408500);上海市高水平地方高校创新团队(SHSMU-ZDCX20212100)

Renewal of esophageal and gastric macrophages by circulating monocytes

ZHU Yiwen¹^,²(), YU Qing¹(), WU Xinrui¹, LU Jie¹, CHEN Zihao¹, GINHOUX Florent², SU Bing¹^,²(), LIU Zhaoyuan¹^,²()

^1.Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
^2.Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China

Received:2022-06-13 Accepted:2022-08-29 Online:2022-09-28 Published:2022-09-28
Contact: SU Bing,LIU Zhaoyuan E-mail:yiwen.zhu@sjtu.edu.cn;1279786056@qq.com;bingsu@sjtu.edu.cn;zhaoyuan_liu@sjtu.edu.cn
Supported by:
National Natural Science Foundation of China(31900630);Shanghai Rising-Star Program(20QA1408500);Innovative Research Team of High-Level Local Universities in Shanghai(SHSMU-ZDCX20212100)

摘要/Abstract

摘要：

目的·揭示单核细胞对食管和胃中巨噬细胞的更新。方法·Ms4a3^Cre -Rosa^TdT 单核细胞示踪模型小鼠的单核细胞携带永久性的tdTomato红色荧光标志物，由这些单核细胞发育产生的巨噬细胞会携带红色荧光，从而与组织中原有的胚胎来源的驻留巨噬细胞区分。通过免疫荧光成像检测不同年龄（2周龄、8周龄和15月龄）Ms4a3^Cre -Rosa^TdT 小鼠食管和胃中携带红色荧光的离子化钙结合适配分子1（ionized calcium-binding adapter molecule 1，IBA1）阳性巨噬细胞的数量和比例，明确单核细胞对食管和胃中巨噬细胞的贡献，以及胚胎和单核细胞2种不同来源巨噬细胞在食管和胃中随年龄的变化。结果·2周龄Ms4a3^Cre -Rosa^TdT 小鼠的食管和胃中，仅有少量巨噬细胞携带红色荧光标志物，说明幼年小鼠的食管和胃中巨噬细胞主要为胚胎时期产生的组织驻留巨噬细胞，单核细胞来源的巨噬细胞数量较少；8周龄成年小鼠的胃中存在大量tdTomato阳性的单核细胞来源的巨噬细胞；15月龄小鼠的食管和胃中，绝大多数的巨噬细胞携带单核细胞的红色荧光标志物，说明老年小鼠的食管和胃中巨噬细胞主要来自循环血液中的单核细胞。结论·幼年小鼠的食管和胃中巨噬细胞主要为胚胎时期产生的驻留巨噬细胞，随着年龄的增长，单核细胞来源的细胞逐渐替换食管和胃中的组织驻留巨噬细胞；老年小鼠食管和胃中巨噬细胞主要来自循环血液中的单核细胞。小鼠食管和胃中巨噬细胞是一个随年龄变化的、由不同比例胚胎来源和单核细胞来源的细胞组成的群体。

关键词: 巨噬细胞, 单核细胞, 谱系示踪, 食管, 胃

Abstract:

Objective ·To reveal the renewal kinetics of esophageal and gastric macrophages by circulating monocytes. Methods ·The monocytes of the Ms4a3^Cre -Rosa^TdT fate mapping model mice carry an irreversible tdTomato red fluorescent marker. The macrophages derived from these monocytes will also carry red fluorescence, distinguishing them from the embryonic-derived macrophages. The contribution of monocytes to esophageal and gastric macrophages was determined by detecting the number and the proportion of red fluorescence labeling in the ionized calcium-binding adapter molecule 1 (IBA1) positive macrophages in the esophagus and stomach from Ms4a3^Cre -Rosa^TdT mice of different ages (2 weeks, 8 weeks and 15 months of age) by immunofluorescence imaging. Results ·In the esophagus and stomach of 2-week-old Ms4a3^Cre -Rosa^TdT mice, most macrophages were tdTomato negative, indicating that the esophageal macrophages and gastric macrophages of young mice were mainly embryonic derived. In 8-week-old adult mice, many tdTomato positive monocyte-derived macrophages could be detected in the stomach. In 15-month-old mice, most of the esophageal and gastric macrophages were tdTomato positive, indicating that the esophagus and stomach macrophages of the old mice were mainly produced by monocytes. Conclusion ·In juvenile mice, esophageal and gastric macrophages are mainly embryonic-derived macrophages, while with age, monocyte-derived macrophages gradually replace tissue-resident macrophages in the esophagus and stomach. Esophageal and gastric macrophages in aged mice are mainly derived from circulating monocytes. Thus, the macrophage pool in the esophagus and stomach of mice consists of embryonic- and mononuclear-derived cells with their proportions changing with age.

Key words: macrophage, monocyte, fate mapping, esophagus, stomach

中图分类号:

R392.1

朱忆文, 于庆, 吴欣睿, 路洁, 陈梓濠, GINHOUX Florent, 苏冰, 刘兆远. 单核细胞对食管和胃中巨噬细胞的更新[J]. 上海交通大学学报（医学版）, 2022, 42(9): 1208-1215.

ZHU Yiwen, YU Qing, WU Xinrui, LU Jie, CHEN Zihao, GINHOUX Florent, SU Bing, LIU Zhaoyuan. Renewal of esophageal and gastric macrophages by circulating monocytes[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022, 42(9): 1208-1215.

图/表 5

图1 食管和胃中巨噬细胞的免疫荧光成像Note： A/B. Immunofluorescence images show the expression of CX3CR1-GFP (green) and IBA1 (purple) in the esophagus (A) and the stomach (B) from Cx3cr1Gfp/+ mice. Nucleuses were counter stained with DAPI (grey). The white arrows indicate intraepithelial macrophages, and the yellow arrows indicate IBA1+ CX3CR1- macrophages.

Fig 1 Immunofluorescence imaging of esophageal and gastric macrophages

图2 2周龄 Ms4a3Cre -RosaTdT 小鼠食管和胃中巨噬细胞的免疫荧光成像Note： A. Schema shows the concept of the experimental design. B. Immunofluorescence images of the esophagus from 2-week-old Ms4a3Cre -RosaTdT mice. C. Immunofluorescence images of the stomach from 2-week-old Ms4a3Cre -RosaTdT mice. Green indicates IBA1; red indicates tdTomato; blue indicates DAPI.

Fig 2 Immunofluorescence imaging of esophageal and gastric macrophages in 2-week-old Ms4a3Cre -RosaTdT mice

图3 8周龄 Ms4a3Cre -RosaTdT 小鼠食管和胃中巨噬细胞的免疫荧光成像Note： A. Immunofluorescence images of the esophagus from 8-week-old Ms4a3Cre -RosaTdT mice. B. Immunofluorescence images of the stomach from 8-week-old Ms4a3Cre -RosaTdT mice. Green indicates IBA1; red indicates tdTomato; blue indicates DAPI.

Fig 3 Immunofluorescence imaging of esophageal and gastric macrophages in 8-week-old Ms4a3Cre -RosaTdT mice

图4 15月龄 Ms4a3Cre -RosaTdT 小鼠食管和胃中巨噬细胞的免疫荧光成像Note： A. Immunofluorescence images of the esophagus from 15-month-old Ms4a3Cre -RosaTdT mice. B. Immunofluorescence images of the stomach from 15-month-old Ms4a3Cre -RosaTdT mice. Green indicates IBA1; red indicates tdTomato; blue indicates DAPI.

Fig 4 Immunofluorescence imaging of esophageal and gastric macrophages in 15-month-old Ms4a3Cre -RosaTdT mice

图5 单核细胞对食管和胃中巨噬细胞的更新示意图

Fig 5 Renewal kinetics of esophageal and gastric macrophages by monocytes

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单核细胞对食管和胃中巨噬细胞的更新

Renewal of esophageal and gastric macrophages by circulating monocytes

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