@article{PernissBoonenTonacketal.2023,
  author    = {Alexander Perniss and Brett Boonen and Sarah Tonack and Moritz Thiel and Krupali Poharkar and Mohamad Wessam Alnouri and Maryam Keshavarz and Tamara Papadakis and Silke Wiegand and Uwe Pfeil and Katrin Richter and Mike Althaus and Johannes Oberwinkler and Burkhard Sch{\"u}tz and Ulrich Boehm and Stefan Offermanns and Trese Leinders-Zufall and Frank Zufall and Wolfgang Kummer},
  title     = {A succinate/SUCNR1-brush cell defense program in the tracheal epithelium},
  series   = {Science Advances},
  volume    = {9},
  number    = {31},
  publisher = {American Association for the Advancement of Science},
  issn      = {2375-2548},
  doi       = {10.1126/sciadv.adg8842},
  url       = {https://nbn-resolving.org/urn:nbn:de:hbz:1044-opus-74794},
  year      = {2023},
  abstract  = {Host-derived succinate accumulates in the airways during bacterial infection. Here, we show that luminal succinate activates murine tracheal brush (tuft) cells through a signaling cascade involving the succinate receptor 1 (SUCNR1), phospholipase Cβ2, and the cation channel transient receptor potential channel subfamily M member 5 (TRPM5). Stimulated brush cells then trigger a long-range Ca2+ wave spreading radially over the tracheal epithelium through a sequential signaling process. First, brush cells release acetylcholine, which excites nearby cells via muscarinic acetylcholine receptors. From there, the Ca2+ wave propagates through gap junction signaling, reaching also distant ciliated and secretory cells. These effector cells translate activation into enhanced ciliary activity and Cl- secretion, which are synergistic in boosting mucociliary clearance, the major innate defense mechanism of the airways. Our data establish tracheal brush cells as a central hub in triggering a global epithelial defense program in response to a danger-associated metabolite.},
  language  = {en}
}