Neutrophils mediate the capture of peritoneal contaminants by fat-associated lymphoid clusters of the omentum

Neutrophils mediate the capture of peritoneal contaminants by fat-associated lymphoid clusters of the omentum
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中性粒细胞介导大网膜脂肪相关淋巴簇捕获腹膜污染物

DOI:
10.1101/774968
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发表时间:
2019
期刊:
--
影响因子:
--
通讯作者:
Jackson-Jones L
Jackson-Jones L
中科院分区:
--
文献类型:
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作者:
Jackson-Jones L

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网膜是一种富含脂肪相关淋巴细胞簇(FALCs)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。通过单细胞RNA测序和大网膜基质细胞的空间分析,我们发现FALC表面覆盖着特化的间皮细胞,我们将其命名为FALC覆盖细胞。我们证明了CXCL1是由FALC覆盖细胞表达的,并且在腹膜炎期间,CXCL1对FALC内中性粒细胞的保留和积累至关重要。我们表明,蛋白精氨酸脱亚胺酶4介导密集中性粒细胞聚集体的形成,这是中和存在于腹膜腔中的颗粒所必需的。最后,我们在急性阑尾炎患者中提供了证实性证据,证明大网膜也是中性粒细胞募集和细菌捕获的场所,因此是免疫防御腹膜污染物传播的重要组成部分。
The omentum is a visceral adipose tissue rich in fat-associated lymphoid clusters (FALCs), which collects peritoneal contaminants and provides a first layer of immunological defence within the abdomen. Using single-cell RNA sequencing and spatial analysis of omental stromal cells, we reveal that the surface of FALCs are covered with specialised mesothelial cells, which we name FALC cover cells. We demonstrate that CXCL1 is expressed by FALC cover cells and that CXCL1 is critical for the retention and accumulation of neutrophils within FALCs during peritonitis. We show that protein arginine deiminase 4 mediates the formation of dense neutrophil aggregates, which are required for the neutralisation of particles present in the peritoneal cavity. Finally, we provide confirmatory evidence in humans with acute appendicitis, that the omentum is also a site of neutrophil recruitment and bacterial capture, and is thus an important component of the immunological defence against the propagation of peritoneal contaminants.
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