Rights statement: This is the author’s version of a work that was accepted for publication in Immunity. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Immunity, 52, 4, 2020 DOI: 10.1016/j.immuni.2020.03.011
Accepted author manuscript, 75.3 MB, PDF document
Available under license: CC BY: Creative Commons Attribution 4.0 International License
Final published version
Licence: CC BY: Creative Commons Attribution 4.0 International License
Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
}
TY - JOUR
T1 - Stromal cells covering omental fat-associated lymphoid clusters trigger the formation of neutrophil aggregates to capture peritoneal contaminants
AU - Jackson-Jones, Lucy
AU - Smith, Peter
AU - Portman, Jordan
AU - Magalhaes, Marlène Sophie
AU - Mylonas, Katie
AU - Vermeren, Matthieu
AU - Nixon, Mark
AU - Henderson, Beth
AU - Dobie, Ross
AU - Vermeren, Sonja
AU - Denby, Laura
AU - Henderson, Neil
AU - Mole, Damian
AU - Bénézech, Cécile
N1 - This is the author’s version of a work that was accepted for publication in Immunity. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Immunity, 52, 4, 2020 DOI: 10.1016/j.immuni.2020.03.011
PY - 2020/4/14
Y1 - 2020/4/14
N2 - 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.
AB - 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.
U2 - 10.1016/j.immuni.2020.03.011
DO - 10.1016/j.immuni.2020.03.011
M3 - Journal article
VL - 52
SP - 700
EP - 715
JO - Immunity
JF - Immunity
SN - 1074-7613
IS - 4
ER -