Author:
Neuenfeldt Friederike,Schumacher Jan Christoph,Grieshaber-Bouyer Ricardo,Habicht Jüri,Schröder-Braunstein Jutta,Gauss Annika,Niesler Beate,Heineken Niko,Dalpke Alexander,Gaida Matthias M.,Giese Thomas,Meuer Stefan,Samstag Yvonne,Wabnitz Guido
Abstract
AbstractCytokines released during chronic inflammatory diseases induce pro-inflammatory properties in polymorphonuclear neutrophils (PMN). Here we show that in vitro cytokine treatment leads to the development of a subgroup of human PMN expressing CCR5, termed CCR5+ cytokine-induced PMN (CCR5+ cPMN). Auto/paracrine TNF signaling increases intracellular neutrophil elastase (ELANE) abundance and induces NETosis in CCR5+ cPMN. Triggering of CCR5 amplifies NETosis. Membranous TNF (mTNF) outside-in signaling induces the formation of reactive oxygen species, a known activator of NETosis. In vivo, we find an increased number of CCR5+ cPMN in the peripheral blood and inflamed lamina propria of patients with ulcerative colitis (UC) but not Crohn’s disease (CD). Notably, failure of anti-TNF therapy is associated with higher frequencies of CCR5+ cPMN. In conclusion, we identify a phenotype of pro-NETotic, CCR5 positive PMN 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.
Publisher
Cold Spring Harbor Laboratory