@article{e35faf38b2fd40509cbfe3388308e86c,
title = "IL-13-programmed airway tuft cells produce PGE2, which promotes CFTR-dependent mucociliary function",
abstract = "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 found that IL-13 expanded and programmed airway tuft cells toward eicosanoid metabolism and that tuft cell deficiency led to a reduction in airway prostaglandin E2 (PGE2) concentration. Allergic airway epithelia bore a signature of PGE2 activation, and PGE2 activation led to cystic fibrosis transmembrane receptor-dependent ion and fluid secretion and accelerated mucociliary transport. These data reveal a role for tuft cells in regulating epithelial mucociliary function in the allergic airway.",
author = "Kotas, {Maya E.} and Moore, {Camille M.} and Gurrola, {Jose G.} and Pletcher, {Steven D.} and Goldberg, {Andrew N.} and Raquel Alvarez and Sheyla Yamato and Bratcher, {Preston E.} and Shaughnessy, {Ciaran A.} and Zeitlin, {Pamela L.} and Zhang, {Irene H.} and Yingchun Li and Montgomery, {Michael T.} and Keehoon Lee and Cope, {Emily K.} and Locksley, {Richard M.} and Seibold, {Max A.} and Gordon, {Erin D.}",
note = "Funding Information: The authors would like to acknowledge Robert Bridges, the Rosalind Franklin University of Medicine, and the Cystic Fibrosis Foundation for the contribution of compounds to this work through the CFTR Chemical Compound Distribution Program. We thank Kyle Marchuk of the Biological Imaging Development CoLab at UCSF Parnassus for training and support for video microscopy and analysis using Imaris. Technical support for single-cell sequencing was provided by the UCSF Institute for Human Genomics. We are grateful to the financial support of the NIH (5P01HL107202-07 to RML and MAS; R01AI026918 to RML; 5R01AI136962 to EDG; R01HL128439, R01HL135156, and P01HL132821 to MAS; F32HL140868 and T32HL007185 to MEK; F32HL158174 to CAS), the Department of Defense (MAS), the Howard Hughes Medical Institute (RML), the A.P. Giannini Foundation (MEK), the Webb-Waring Early Career Investigator Award from the Boettcher Foundation (CMM), the Nina Ireland Program for Lung Health at UCSF (EDG), the UCSF John A. Watson Faculty Scholar Fund (JGG), the SABRE Center at UCSF (RML and EDG), the Cystic Fibrosis Foundation (PEB and PLZ), and the Eugene F. and Easton M. Crawford Charitable Lead Unitrust (CAS and PEB). This work would not have been possible without the support and participation of our patients. Publisher Copyright: {\textcopyright} 2022, Kotas et al.",
year = "2022",
month = jul,
day = "8",
doi = "10.1172/jci.insight.159832",
language = "English (US)",
volume = "7",
journal = "JCI insight",
issn = "2379-3708",
publisher = "The American Society for Clinical Investigation",
number = "13",
}