Stromal Cells Covering Omental Fat-Associated Lymphoid Clusters Trigger Formation of Neutrophil Aggregates to Capture Peritoneal Contaminants

Lucy Helen Jackson-Jones, Peter Smith, Jordan Raymond Portman, Marlène Sophie Magalhaes, Katie Jude Mylonas, Matthieu Marie Vermeren, Mark Nixon, Beth Emily Pollot Henderson, Ross Dobie, Sonja Vermeren, Laura Denby, Neil Cowan Henderson, Damian James Mole, Cécile Bénézech

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)700-715.e6
JournalImmunity
Volume52
Issue number4
Early online date14 Apr 2020
DOIs
Publication statusPublished - 14 Apr 2020

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