Centre for Cardiovascular Science, University of Edinburgh, Edinburgh EH16 4TJ, UK; Division of Biomedical and Life Sciences, Lancaster University, Lancaster LA1 4YQ, UK.
Centre for Cardiovascular Science, University of Edinburgh, Edinburgh EH16 4TJ, UK.
Immunity. 2020 Apr 14;52(4):700-715.e6. doi: 10.1016/j.immuni.2020.03.011.
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.
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，并为腹部提供第一道免疫防御。在这里，我们研究了介导腹膜炎期间腹膜污染物捕获的机制。对网膜基质细胞的单细胞 RNA 测序和空间分析表明，FALC 的表面被 CXCL1 间皮细胞覆盖，我们将其称为 FALC 覆盖细胞。在酵母聚糖诱导的腹膜炎期间，阻断 CXCL1 可抑制 FALC 处中性粒细胞的募集和聚集。对蛋白精氨酸脱亚氨酶 4 的抑制，这种酶对于释放中性粒细胞胞外陷阱至关重要，可消除中性粒细胞聚集和网膜 FALC 对腹膜污染物的捕获。对急性阑尾炎患者网膜样本的分析证实了 FALC 处中性粒细胞的募集和细菌捕获。因此，专门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。
