| First Author | Perniss A | Year | 2023 |
| Journal | Sci Adv | Volume | 9 |
| Issue | 31 | Pages | eadg8842 |
| PubMed ID | 37531421 | Mgi Jnum | J:342584 |
| Mgi Id | MGI:7515853 | Doi | 10.1126/sciadv.adg8842 |
| Citation | Perniss A, et al. (2023) A succinate/SUCNR1-brush cell defense program in the tracheal epithelium. Sci Adv 9(31):eadg8842 |
| abstractText | 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 Cbeta2, and the cation channel transient receptor potential channel subfamily M member 5 (TRPM5). Stimulated brush cells then trigger a long-range Ca(2+) 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 Ca(2+) 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. |
