2. Academic Validation
  3. Pulmonary neuroendocrine cells sense succinate to stimulate myoepithelial cell contraction

Pulmonary neuroendocrine cells sense succinate to stimulate myoepithelial cell contraction

  • Dev Cell. 2022 Sep 26;57(18):2221-2236.e5. doi: 10.1016/j.devcel.2022.08.010.
Wenjie Yu 1,  Thomas O Moninger 2,  Michael V Rector 2,  David A Stoltz 3,  Michael J Welsh 4
Affiliations

Affiliations

  • 1 Department of Internal Medicine and Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; Howard Hughes Medical Institute, University of Iowa, Iowa City, IA 52242, USA.
  • 2 Department of Internal Medicine and Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
  • 3 Department of Internal Medicine and Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; Department of Molecular Physiology and Biophysics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; Roy J. Carver Department of Biomedical Engineering, College of Engineering, University of Iowa, Iowa City, IA 52242, USA.
  • 4 Department of Internal Medicine and Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; Department of Molecular Physiology and Biophysics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; Howard Hughes Medical Institute, University of Iowa, Iowa City, IA 52242, USA. Electronic address: michael-welsh@uiowa.edu.
PMID: 36108628 DOI: 10.1016/j.devcel.2022.08.010
Abstract

Pulmonary neuroendocrine cells (PNECs) are rare airway cells with potential sensory capacity linked to vagal neurons and immune cells. How PNECs sense and respond to external stimuli remains poorly understood. We discovered PNECs located within pig and human submucosal glands, a tissue that produces much of the mucus that defends the lung. These PNECs sense succinate, an inflammatory molecule in liquid lining the airway surface. The results indicate that succinate migrates down the submucosal gland duct to the acinus, where it triggers apical succinate receptors, causing PNECs to release ATP. The short-range ATP signal stimulates the contraction of myoepithelial cells wrapped tightly around the submucosal glands. Succinate-triggered gland contraction may complement the action of neurotransmitters that induce mucus release but not gland contraction to promote mucus ejection onto the airway surface. These findings identify a local circuit in which rare PNECs within submucosal glands sense an environmental cue to orchestrate the function of airway glands.

Keywords

ATP; P2Y1 receptor; SUCNR1; airway submucosal gland; cystic fibrosis; mucus; myoepithelial cell; pulmonary neuroendocrine cell; succinate.

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