Stromal cells covering omental fat-associated lymphoid clusters trigger the formation of neutrophil aggregates to capture peritoneal contaminants

Jackson-Jones, Lucy and Smith, Peter and Portman, Jordan and Magalhaes, Marlène Sophie and Mylonas, Katie and Vermeren, Matthieu and Nixon, Mark and Henderson, Beth and Dobie, Ross and Vermeren, Sonja and Denby, Laura and Henderson, Neil and Mole, Damian and Bénézech, Cécile (2020) Stromal cells covering omental fat-associated lymphoid clusters trigger the formation of neutrophil aggregates to capture peritoneal contaminants. Immunity, 52 (4). pp. 700-715. ISSN 1074-7613

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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.