Stromal Cells Covering Omental Fat-Associated Lymphoid Clusters Trigger Formation of Neutrophil Aggregates to Capture Peritoneal Contaminants
Stromal Cells Covering Omental Fat-Associated Lymphoid Clusters Trigger Formation of Neutrophil Aggregates to Capture Peritoneal Contaminants
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DOI：
10.1016/j.immuni.2020.03.011
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发表时间：
2020-04-14
期刊：
影响因子：
32.4
通讯作者：
Benezech, Cecile
中科院分区：
文献类型：
--
作者：
Jackson-Jones, Lucy Helen;Smith, Peter;Benezech, Cecile
大网膜是一种富含脂肪相关淋巴簇（fat-associated lymphoid clusters，缩写为PBMC）的内脏脂肪组织，它收集腹膜污染物，并在腹部提供第一层免疫防御。在这里，我们研究了腹膜炎期间介导腹膜污染物捕获的机制。网膜基质细胞的单细胞RNA测序和空间分析显示，CXCL1（+）间皮细胞覆盖着CXCL1（+）间皮细胞，我们称之为CXCL1（+）间皮细胞。阻断CXCL1可抑制酵母多糖诱导的腹膜炎过程中中性粒细胞在腹膜透析液中的募集和聚集。蛋白质精氨酸脱亚胺酶4，一种对中性粒细胞胞外陷阱的释放很重要的酶的抑制，废除了中性粒细胞的聚集和腹膜污染物被网膜CANCs捕获。对急性阑尾炎患者网膜样本的分析证实了中性粒细胞的募集和细菌在阑尾炎细胞中的捕获。因此，特化的网膜间皮细胞协调中性粒细胞的募集和聚集以捕获腹膜污染物。
The omentum is a visceral adipose tissue rich in fat-associated lymphoid clusters (FALCs) that collects peritoneal contaminants and provides a first layer of immunological defense within the abdomen. Here, we investigated the mechanisms that mediate the capture of peritoneal contaminants during peritonitis. Single-cell RNA sequencing and spatial analysis of omental stromal cells revealed that the surface of FALCs were covered by CXCL1(+) mesothelial cells, which we termed FALC cover cells. Blockade of CXCL1 inhibited the recruitment and aggregation of neutrophils at FALCs during zymosan-induced peritonitis. Inhibition of protein arginine deiminase 4, an enzyme important for the release of neutrophil extracellular traps, abolished neutrophil aggregation and the capture of peritoneal contaminants by omental FALCs. Analysis of omental samples from patients with acute appendicitis confirmed neutrophil recruitment and bacterial capture at FALCs. Thus, specialized omental mesothelial cells coordinate the recruitment and aggregation of neutrophils to capture peritoneal contaminants.