biostudies-literatureJordan PMDeutsche ForschungsgemeinschaftInterdisziplinäres Zentrum für Klinische Forschung, Universitätsklinikum Jena541-554https://www.ebi.ac.uk/biostudies/studies/S-EPMC8517600biostudies-literatureUnknown164(3)IL-33 and ATP are alarmins, which are released upon damage of cellular barriers or are actively secreted upon cell stress. Due to high-density expression of the IL-33 receptor T1/ST2 (IL-33R), and the ATP receptor P2X7, mast cells (MCs) are one of the first highly sensitive sentinels recognizing released IL-33 or ATP in damaged peripheral tissues. Whereas IL-33 induces the MyD88-dependent activation of the TAK1-IKK2-NF-κB signalling, ATP induces the Ca²⁺ -dependent activation of NFAT. Thereby, each signal alone only induces a moderate production of pro-inflammatory cytokines and lipid mediators (LMs). However, MCs, which simultaneously sense (co-sensing) IL-33 and ATP, display an enhanced and prolonged activation of the TAK1-IKK2-NF-κB signalling pathway. This resulted in a massImmunologyATP/IL-33-triggered hyperactivation of mast cells results in an amplified production of pro-inflammatory cytokines and eicosanoids.PMC8517600DFG DR1113/1-1CRC854/A28N316213987SFB1278/1IZKF-MSP-1DFG DR1113/1‐1RTG 2408/TP4Groth MDudeck ADrube SKuchler CSerfling EJordan PMWeber FAndreas NJager UWegner PKamradt TWerz OfalseATP/IL-33-triggered hyperactivation of mast cells results in an amplified production of pro-inflammatory cytokines and eicosanoids.IL-33 and ATP are alarmins, which are released upon damage of cellular barriers or are actively secreted upon cell stress. Due to high-density expression of the IL-33 receptor T1/ST2 (IL-33R), and the ATP receptor P2X7, mast cells (MCs) are one of the first highly sensitive sentinels recognizing released IL-33 or ATP in damaged peripheral tissues. Whereas IL-33 induces the MyD88-dependent activation of the TAK1-IKK2-NF-κB signalling, ATP induces the Ca²⁺ -dependent activation of NFAT. Thereby, each signal alone only induces a moderate production of pro-inflammatory cytokines and lipid mediators (LMs). However, MCs, which simultaneously sense (co-sensing) IL-33 and ATP, display an enhanced and prolonged activation of the TAK1-IKK2-NF-κB signalling pathway. This resulted in a mass2021-01-01T00:00:00Z2021 Nov2025-04-22T11:27:09.355Z2025-04-06T00:01:09.754ZS-EPMC85176003414237010.1111/imm.13386