2025-03-24 マウントサイナイ医療システム(MSHS)
<関連情報>
- https://www.mountsinai.org/about/newsroom/2025/mount-sinai-researchers-identify-key-gut-sensor-that-regulates-digestion-and-immunity
- https://www.sciencedirect.com/science/article/pii/S0092867425002582?dgcid=coauthor
腸管神経細胞Piezo1は、力を感知することで力学的・免疫学的恒常性を維持する Enteric neuronal Piezo1 maintains mechanical and immunological homeostasis by sensing force
Zili Xie, Lillian Rose, Jing Feng, Yonghui Zhao, Yisi Lu, Harry Kane, Timothy J. Hibberd, Xueming Hu, Zhen Wang, Kaikai Zang, Xingliang Yang, Quentin Richardson, Rahmeh Othman, Olivia Venezia, Ademi Zhakyp, Fang Gao, Nobuya Abe, Keren Vigeland, Hongshen Wang, Camren Branch …Ruaidhrí Jackson
Cell Available online 24 March 2025
DOI:https://doi.org/10.1016/j.cell.2025.02.031
Graphical abstract
Highlights
- The enteric nervous system directly senses mechanical force via Piezo1
- Cholinergic enteric neurons functionally express the Piezo1 mechanosensor
- Piezo1 on cholinergic neurons is required to accelerate GI motility in response to force
- Cholinergic neuronal Piezo1-mechanosensation limits aberrant intestinal inflammation
Summary
The gastrointestinal (GI) tract experiences a myriad of mechanical forces while orchestrating digestion and barrier immunity. A central conductor of these processes, the enteric nervous system (ENS), detects luminal pressure to regulate peristalsis independently of extrinsic input from the central and peripheral nervous systems. However, how the ∼500 million enteric neurons that reside in the GI tract sense and respond to force remains unknown. Herein, we establish that the mechanosensor Piezo1 is functionally expressed in cholinergic enteric neurons. Optogenetic stimulation of Piezo1+ cholinergic enteric neurons drives colonic motility, while Piezo1 deficiency reduces cholinergic neuronal activity and slows peristalsis. Additionally, Piezo1 deficiency in cholinergic enteric neurons abolishes exercise-induced acceleration of GI motility. Finally, we uncover that enteric neuronal Piezo1 function is required for motility alterations in colitis and acts to prevent aberrant inflammation and tissue damage. This work uncovers how the ENS senses and responds to mechanical force.
