Wicki, SimoneSimoneWickiGurzeler, UrsinaUrsinaGurzelerCorazza, NadiaNadiaCorazzaGenitsch, VeraVeraGenitschWong, Wendy Wei-LynnWendy Wei-LynnWongKaufmann, ThomasThomasKaufmann0000-0001-9906-874X2024-10-252024-10-252018-02-28https://boris-portal.unibe.ch/handle/20.500.12422/159195Neutrophils are key players in the early defense against invading pathogens. Due to their potent effector functions, programmed cell death of activated neutrophils has to be tightly controlled; however, its underlying mechanisms remain unclear. Fas ligand (FASL/CD95L) has been shown to induce neutrophil apoptosis, which is accelerated by the processing of the BH3-only protein BH3 interacting domain death agonist (BID) to trigger mitochondrial apoptotic events, and been attributed a regulatory role during viral and bacterial infections. Here, we show that, in accordance with previous works, mouse neutrophils underwent caspase-dependent apoptosis in response to FASL, and that this cell death was significantly delayed upon loss of BID. However, pan-caspase inhibition failed to protect mouse neutrophils from FASL-induced apoptosis and caused a switch to RIPK3-dependent necroptotic cell death. Intriguingly, such a switch was less evident in the absence of BID, particularly under inflammatory conditions. Delayed neutrophil apoptosis has been implicated in several auto-inflammatory diseases, including inflammatory bowel disease. We show that neutrophil and macrophage driven acute dextran sulfate sodium (DSS) induced colitis was slightly more aggravated in BID-deficient mice, based on significantly increased weight loss compared to wild-type controls. Taken together, our data support a central role for FASL > FAS and BID in mouse neutrophil cell death and further underline the anti-inflammatory role of BID.enBID FAS/CD95 RIPK3 apoptosis caspases colitis inflammation mouse model necroptosis neutrophil600 - Technology::610 - Medicine & healtharticle10.7892/boris.1125982949559510.3390/ijms19030684