Inflammation induces pro-NETotic neutrophils via TNFR2 signaling

Neuenfeldt F, Schumacher JC, Grieshaber-Bouyer R, Habicht J, Schröder-Braunstein J, Gauss A, Merle U, Niesler B, Heineken N, Dalpke A, Gaida MM, Giese T, Meuer S, Samstag Y, Wabnitz G (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Cell Reports Elsevier (Cell Press)

Book Volume: 39

Article Number: 110710

Journal Issue: 3

DOI: 10.1016/j.celrep.2022.110710

Abstract

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.

Authors with CRIS profile

Ricardo Grieshaber Bouyer

Involved external institutions

Ruprecht-Karls-Universität Heidelberg DE Germany (DE) Universitätsklinikum Heidelberg DE Germany (DE) Universitätsklinikum Carl Gustav Carus Dresden DE Germany (DE) Universitätsmedizin der Johannes Gutenberg-Universität Mainz DE Germany (DE)

How to cite

APA:

Neuenfeldt, F., Schumacher, J.C., Grieshaber-Bouyer, R., Habicht, J., Schröder-Braunstein, J., Gauss, A.,... Wabnitz, G. (2022). Inflammation induces pro-NETotic neutrophils via TNFR2 signaling. Cell Reports, 39(3). https://doi.org/10.1016/j.celrep.2022.110710

MLA:

Neuenfeldt, Friederike, et al. "Inflammation induces pro-NETotic neutrophils via TNFR2 signaling." Cell Reports 39.3 (2022).

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