IL-13-programmed airway tuft cells produce PGE2, which promotes CFTR-dependent mucociliary function

Maya E Kotas; Camille M. Moore; Jose G. Gurrola II; Steven D. Pletcher; Andrew N. Goldberg; Raquel Alvarez; Sheyla Yamato; Preston E. Bratcher; Ciaran A. Shaughnessy; Pamela L. Zeitlin; Irene H Zhang; Yingchun Li; Michael T. Montgomery; Keehoon Lee; Emily K. Cope; Richard M. Locksley; Max A. Seibold; Erin D. Gordon

doi:10.1172/jci.insight.159832

¹Department of Medicine, UCSF, San Francisco, United States of America

²Center for Genes, Environment and Health, National Jewish Health, Denver, United States of America

³Department of Otolaryngology, UCSF, San Francisco, United States of America

⁴Department of Pediatrics, National Jewish Health, Denver, United States of America

⁵Department of Pediatrics, National Jewish Health, Baltimore, United States of America

⁶Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, United States of America

⁷Department of Medicine, National Jewish Health, Denver, United States of America

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¹Department of Medicine, UCSF, San Francisco, United States of America

²Center for Genes, Environment and Health, National Jewish Health, Denver, United States of America

³Department of Otolaryngology, UCSF, San Francisco, United States of America

⁴Department of Pediatrics, National Jewish Health, Denver, United States of America

⁵Department of Pediatrics, National Jewish Health, Baltimore, United States of America

⁶Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, United States of America

⁷Department of Medicine, National Jewish Health, Denver, United States of America

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¹Department of Medicine, UCSF, San Francisco, United States of America

²Center for Genes, Environment and Health, National Jewish Health, Denver, United States of America

³Department of Otolaryngology, UCSF, San Francisco, United States of America

⁴Department of Pediatrics, National Jewish Health, Denver, United States of America

⁵Department of Pediatrics, National Jewish Health, Baltimore, United States of America

⁶Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, United States of America

⁷Department of Medicine, National Jewish Health, Denver, United States of America

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¹Department of Medicine, UCSF, San Francisco, United States of America

²Center for Genes, Environment and Health, National Jewish Health, Denver, United States of America

³Department of Otolaryngology, UCSF, San Francisco, United States of America

⁴Department of Pediatrics, National Jewish Health, Denver, United States of America

⁵Department of Pediatrics, National Jewish Health, Baltimore, United States of America

⁶Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, United States of America

⁷Department of Medicine, National Jewish Health, Denver, United States of America

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¹Department of Medicine, UCSF, San Francisco, United States of America

²Center for Genes, Environment and Health, National Jewish Health, Denver, United States of America

³Department of Otolaryngology, UCSF, San Francisco, United States of America

⁴Department of Pediatrics, National Jewish Health, Denver, United States of America

⁵Department of Pediatrics, National Jewish Health, Baltimore, United States of America

⁶Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, United States of America

⁷Department of Medicine, National Jewish Health, Denver, United States of America

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¹Department of Medicine, UCSF, San Francisco, United States of America

²Center for Genes, Environment and Health, National Jewish Health, Denver, United States of America

³Department of Otolaryngology, UCSF, San Francisco, United States of America

⁴Department of Pediatrics, National Jewish Health, Denver, United States of America

⁵Department of Pediatrics, National Jewish Health, Baltimore, United States of America

⁶Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, United States of America

⁷Department of Medicine, National Jewish Health, Denver, United States of America

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¹Department of Medicine, UCSF, San Francisco, United States of America

²Center for Genes, Environment and Health, National Jewish Health, Denver, United States of America

³Department of Otolaryngology, UCSF, San Francisco, United States of America

⁴Department of Pediatrics, National Jewish Health, Denver, United States of America

⁵Department of Pediatrics, National Jewish Health, Baltimore, United States of America

⁶Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, United States of America

⁷Department of Medicine, National Jewish Health, Denver, United States of America

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¹Department of Medicine, UCSF, San Francisco, United States of America

²Center for Genes, Environment and Health, National Jewish Health, Denver, United States of America

³Department of Otolaryngology, UCSF, San Francisco, United States of America

⁴Department of Pediatrics, National Jewish Health, Denver, United States of America

⁵Department of Pediatrics, National Jewish Health, Baltimore, United States of America

⁶Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, United States of America

⁷Department of Medicine, National Jewish Health, Denver, United States of America

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¹Department of Medicine, UCSF, San Francisco, United States of America

²Center for Genes, Environment and Health, National Jewish Health, Denver, United States of America

³Department of Otolaryngology, UCSF, San Francisco, United States of America

⁴Department of Pediatrics, National Jewish Health, Denver, United States of America

⁵Department of Pediatrics, National Jewish Health, Baltimore, United States of America

⁶Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, United States of America

⁷Department of Medicine, National Jewish Health, Denver, United States of America

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¹Department of Medicine, UCSF, San Francisco, United States of America

²Center for Genes, Environment and Health, National Jewish Health, Denver, United States of America

³Department of Otolaryngology, UCSF, San Francisco, United States of America

⁴Department of Pediatrics, National Jewish Health, Denver, United States of America

⁵Department of Pediatrics, National Jewish Health, Baltimore, United States of America

⁶Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, United States of America

⁷Department of Medicine, National Jewish Health, Denver, United States of America

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¹Department of Medicine, UCSF, San Francisco, United States of America

²Center for Genes, Environment and Health, National Jewish Health, Denver, United States of America

³Department of Otolaryngology, UCSF, San Francisco, United States of America

⁴Department of Pediatrics, National Jewish Health, Denver, United States of America

⁵Department of Pediatrics, National Jewish Health, Baltimore, United States of America

⁶Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, United States of America

⁷Department of Medicine, National Jewish Health, Denver, United States of America

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¹Department of Medicine, UCSF, San Francisco, United States of America

²Center for Genes, Environment and Health, National Jewish Health, Denver, United States of America

³Department of Otolaryngology, UCSF, San Francisco, United States of America

⁴Department of Pediatrics, National Jewish Health, Denver, United States of America

⁵Department of Pediatrics, National Jewish Health, Baltimore, United States of America

⁶Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, United States of America

⁷Department of Medicine, National Jewish Health, Denver, United States of America

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¹Department of Medicine, UCSF, San Francisco, United States of America

²Center for Genes, Environment and Health, National Jewish Health, Denver, United States of America

³Department of Otolaryngology, UCSF, San Francisco, United States of America

⁴Department of Pediatrics, National Jewish Health, Denver, United States of America

⁵Department of Pediatrics, National Jewish Health, Baltimore, United States of America

⁶Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, United States of America

⁷Department of Medicine, National Jewish Health, Denver, United States of America

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¹Department of Medicine, UCSF, San Francisco, United States of America

²Center for Genes, Environment and Health, National Jewish Health, Denver, United States of America

³Department of Otolaryngology, UCSF, San Francisco, United States of America

⁴Department of Pediatrics, National Jewish Health, Denver, United States of America

⁵Department of Pediatrics, National Jewish Health, Baltimore, United States of America

⁶Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, United States of America

⁷Department of Medicine, National Jewish Health, Denver, United States of America

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¹Department of Medicine, UCSF, San Francisco, United States of America

²Center for Genes, Environment and Health, National Jewish Health, Denver, United States of America

³Department of Otolaryngology, UCSF, San Francisco, United States of America

⁴Department of Pediatrics, National Jewish Health, Denver, United States of America

⁵Department of Pediatrics, National Jewish Health, Baltimore, United States of America

⁶Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, United States of America

⁷Department of Medicine, National Jewish Health, Denver, United States of America

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¹Department of Medicine, UCSF, San Francisco, United States of America

²Center for Genes, Environment and Health, National Jewish Health, Denver, United States of America

³Department of Otolaryngology, UCSF, San Francisco, United States of America

⁴Department of Pediatrics, National Jewish Health, Denver, United States of America

⁵Department of Pediatrics, National Jewish Health, Baltimore, United States of America

⁶Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, United States of America

⁷Department of Medicine, National Jewish Health, Denver, United States of America

Find articles by Locksley, R. in: JCI | PubMed | Google Scholar |

¹Department of Medicine, UCSF, San Francisco, United States of America

²Center for Genes, Environment and Health, National Jewish Health, Denver, United States of America

³Department of Otolaryngology, UCSF, San Francisco, United States of America

⁴Department of Pediatrics, National Jewish Health, Denver, United States of America

⁵Department of Pediatrics, National Jewish Health, Baltimore, United States of America

⁶Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, United States of America

⁷Department of Medicine, National Jewish Health, Denver, United States of America

Find articles by Seibold, M. in: JCI | PubMed | Google Scholar |

¹Department of Medicine, UCSF, San Francisco, United States of America

²Center for Genes, Environment and Health, National Jewish Health, Denver, United States of America

³Department of Otolaryngology, UCSF, San Francisco, United States of America

⁴Department of Pediatrics, National Jewish Health, Denver, United States of America

⁵Department of Pediatrics, National Jewish Health, Baltimore, United States of America

⁶Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, United States of America

⁷Department of Medicine, National Jewish Health, Denver, United States of America

Find articles by Gordon, E. in: JCI | PubMed | Google Scholar |

JCI Insight. https://doi.org/10.1172/jci.insight.159832.
Copyright © 2022, Kotas et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Published May 24, 2022 - Version history

Chronic type 2 (T2) inflammatory diseases of the respiratory tract are characterized by mucus overproduction and disordered mucociliary function, which are largely attributed to the effects of IL-13 on common epithelial cell types (mucus secretory and ciliated cells). The role of rare cells in airway T2 inflammation is less clear, though tuft cells have been shown to be critical in the initiation of T2 immunity in the intestine. Using bulk and single cell RNA sequencing of airway epithelium and mouse modeling, we find that IL-13 expands and programs airway tuft cells towards eicosanoid metabolism, and that tuft cell deficiency leads to a reduction in airway prostaglandin E2 (PGE2)concentration. Allergic airway epithelia bear a signature of prostaglandin E2 activation, and PGE2 activation leads to CFTR-dependent ion and fluid secretion and accelerated mucociliary transport. Together these data reveal a role for tuft cells in regulating epithelial mucociliary function in the allergic airway.

IL-13-programmed airway tuft cells produce PGE2, which promotes CFTR-dependent mucociliary function

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IL-13-programmed airway tuft cells produce PGE2, which promotes CFTR-dependent mucociliary function

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