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...
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| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
April 19, 2022
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| 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 |
| 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 |
| 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. |
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| Item Description: | Gesehen am 09.06.2022 |
| Physical Description: | Online Resource |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2022.110710 |