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Published on: July 20, 2019
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Inflammation induces pro-NETotic neutrophils via TNFR2 signaling
Friederike Neuenfeldt1, Jan Christoph Schumacher1, Ricardo Grieshaber-Bouyer2
1Institute of Immunology, Heidelberg University, Im Neuenheimer Feld 305, 69120 Heidelberg, Germany.
Cell Reports
|April 20, 2022
Summary
Researchers identified a new subgroup of human polymorphonuclear neutrophils (PMNs) called CCR5+ PMNs. These cells promote inflammation and tissue damage in chronic inflammatory diseases like ulcerative colitis.
Area of Science:
- Immunology
- Cell Biology
Background:
- Chronic inflammatory diseases involve cytokines that enhance pro-inflammatory functions of polymorphonuclear neutrophils (PMNs).
- A specific subset of human PMNs expressing CCR5 has been identified.
Purpose of the Study:
- To characterize the pro-inflammatory properties of CCR5+ PMNs.
- To investigate the role of CCR5+ PMNs in chronic inflammatory diseases, specifically ulcerative colitis (UC).
Main Methods:
- Characterization of CCR5+ PMNs in vitro, including analysis of tumor necrosis factor (TNF) signaling, neutrophil elastase (ELANE) abundance, and neutrophil extracellular traps (NETosis) formation.
- Assessment of CCR5+ PMN frequencies in peripheral blood and inflamed tissue from UC patients.
- Correlation of CCR5+ PMN frequencies with anti-TNF therapy response.
Main Results:
- CCR5+ PMNs exhibit increased intracellular ELANE and enhanced NETosis, amplified by CCR5 triggering and TNF signaling.
- Membranous TNF signaling in CCR5+ PMNs induces reactive oxygen species, further promoting NETosis.
- Increased CCR5+ PMN numbers were observed in the peripheral blood and inflamed lamina propria of UC patients.
- Higher frequencies of CCR5+ PMNs were associated with a lack of response to anti-TNF therapy.
Conclusions:
- A pro-NETotic phenotype of CCR5+ PMNs has been identified, present in inflamed tissues and inducible in vitro.
- These CCR5+ PMNs represent a significant factor in tissue damage during chronic inflammation.
- CCR5+ PMNs may serve as a valuable diagnostic marker for chronic inflammatory conditions.
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