Inflammation induces pro-NETotic neutrophils via TNFR2 signaling

Cytokines released during chronic inflammatory diseases induce pro-inflammatory properties in polymorphonuclear neutrophils (PMNs). Here, we describe the development of a subgroup of human PMNs expressing CCR5, termed CCR5+ PMNs. Auto- and paracrine tumor necrosis factor (TNF) signaling increases in...

Full description

Saved in:
Bibliographic Details
Main Authors: Neuenfeldt, Friederike S. (Author) , Schumacher, Jan-Christoph (Author) , Grieshaber-Bouyer, Ricardo (Author) , Habicht, Jüri (Author) , Schröder-Braunstein, Jutta (Author) , Gauss, Annika (Author) , Merle, Uta (Author) , Niesler, Beate (Author) , Heineken, Niko (Author) , Dalpke, Alexander (Author) , Gaida, Matthias (Author) , Giese, Thomas (Author) , Meuer, Stefan (Author) , Samstag, Yvonne (Author) , Wabnitz, Guido H. (Author)
Format: Article (Journal)
Language:English
Published: April 19, 2022
In: Cell reports
Year: 2022, Volume: 39, Issue: 3, Pages: 1-22
ISSN:2211-1247
DOI:10.1016/j.celrep.2022.110710
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.celrep.2022.110710
Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S2211124722004715
Get full text
Author Notes:Friederike Neuenfeldt, Jan Christoph Schumacher, Ricardo Grieshaber-Bouyer, Jüri Habicht, Jutta Schröder-Braunstein, Annika Gauss, Uta Merle, Beate Niesler, Niko Heineken, Alexander Dalpke, Matthias M. Gaida, Thomas Giese, Stefan Meuer, Yvonne Samstag, and Guido Wabnitz
Description
Summary:Cytokines released during chronic inflammatory diseases induce pro-inflammatory properties in polymorphonuclear neutrophils (PMNs). Here, we describe the development of a subgroup of human PMNs expressing CCR5, termed CCR5+ PMNs. Auto- and paracrine tumor necrosis factor (TNF) signaling increases intracellular neutrophil elastase (ELANE) abundance and induces neutrophil extracellular traps formation (NETosis) in CCR5+ PMNs, and triggering of CCR5 amplifies NETosis. Membranous TNF (mTNF) outside-in signaling induces the formation of reactive oxygen species, known activators of NETosis. In vivo, we find an increased number of CCR5+ PMNs in the peripheral blood and inflamed lamina propria of patients with ulcerative colitis (UC). Notably, failure of anti-TNF therapy is associated with higher frequencies of CCR5+ PMNs. In conclusion, we identify a phenotype of pro-NETotic, CCR5+ PMNs present in inflamed tissue in vivo and inducible in vitro. These cells may reflect an important component of tissue damage during chronic inflammation and could be of diagnostic value.
Item Description:Gesehen am 09.06.2022
Physical Description:Online Resource
ISSN:2211-1247
DOI:10.1016/j.celrep.2022.110710