TY  - JOUR
U1  - Zeitschriftenartikel, wissenschaftlich - begutachtet (reviewed)
A1  - Perniss, Alexander
A1  - Boonen, Brett
A1  - Tonack, Sarah
A1  - Thiel, Moritz
A1  - Poharkar, Krupali
A1  - Alnouri, Mohamad Wessam
A1  - Keshavarz, Maryam
A1  - Papadakis, Tamara
A1  - Wiegand, Silke
A1  - Pfeil, Uwe
A1  - Richter, Katrin
A1  - Althaus, Mike
A1  - Oberwinkler, Johannes
A1  - Schütz, Burkhard
A1  - Boehm, Ulrich
A1  - Offermanns, Stefan
A1  - Leinders-Zufall, Trese
A1  - Zufall, Frank
A1  - Kummer, Wolfgang
T1  - A succinate/SUCNR1-brush cell defense program in the tracheal epithelium
JF  - Science Advances
N2  - 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.
UN  - https://nbn-resolving.org/urn:nbn:de:hbz:1044-opus-74794
SN  - 2375-2548
SS  - 2375-2548
U6  - https://doi.org/10.1126/sciadv.adg8842
DO  - https://doi.org/10.1126/sciadv.adg8842
PM  - 37531421
VL  - 9
IS  - 31
SP  - 20
S1  - 20
PB  - American Association for the Advancement of Science
ER  -