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Stromal Cells Covering Omental Fat-Associated Lymphoid Clusters Trigger Formation of Neutrophil Aggregates to Capture Peritoneal Contaminants.
Immunity ( IF 32.4 ) Pub Date : 2020-04-14 , DOI: 10.1016/j.immuni.2020.03.011
Lucy Helen Jackson-Jones 1 , Peter Smith 2 , Jordan Raymond Portman 3 , Marlène Sophie Magalhaes 2 , Katie Jude Mylonas 4 , Matthieu Marie Vermeren 5 , Mark Nixon 2 , Beth Emily Pollot Henderson 3 , Ross Dobie 3 , Sonja Vermeren 3 , Laura Denby 2 , Neil Cowan Henderson 6 , Damian James Mole 3 , Cécile Bénézech 2
Affiliation  

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.

中文翻译:

覆盖大网膜脂肪相关淋巴样簇的基质细胞触发中性粒细胞聚集体的形成以捕获腹膜污染物。

大网膜是富含脂肪相关淋巴簇 (FALC) 的内脏脂肪组织,可收集腹膜污染物并在腹部提供第一层免疫防御。在这里,我们研究了在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 FALC 的表面被 CXCL1+ 间皮细胞覆盖,我们称之为 FALC 覆盖细胞。在酵母聚糖诱导的腹膜炎期间,CXCL1 的阻断抑制了中性粒细胞在 FALC 处的募集和聚集。抑制蛋白质精氨酸脱亚胺酶 4(一种对释放中性粒细胞胞外陷阱很重要的酶)可消除中性粒细胞聚集和网膜 FALC 捕获腹膜污染物。对急性阑尾炎患者的网膜样本的分析证实了中性粒细胞募集和 FALC 的细菌捕获。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。
更新日期:2020-04-21
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