1. Tuft cells are required for a rhinovirus-induced asthma phenotype in immature mice.
- Author
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Li Y, Han M, Singh S, Breckenridge HA, Kreger JE, Stroupe CC, Sawicky DA, Kuo S, Goldsmith AM, Ke F, Shenoy AT, Bentley JK, Matsumoto I, and Hershenson MB
- Subjects
- Animals, Mice, Immunity, Innate, Rhinovirus, Tuft Cells, Lymphocytes metabolism, Mice, Inbred C57BL, Inflammation, Phenotype, Metaplasia, Asthma metabolism, Enterovirus Infections
- Abstract
Infection of immature mice with rhinovirus (RV) induces an asthma-like phenotype consisting of type 2 inflammation, mucous metaplasia, eosinophilic inflammation, and airway hyperresponsiveness that is dependent on IL-25 and type 2 innate lymphoid cells (ILC2s). Doublecortin-like kinase 1-positive (DCLK1+) tuft cells are a major source of IL-25. We sought to determine the requirement of tuft cells for the RV-induced asthma phenotype in wild-type mice and mice deficient in Pou2f3, a transcription factor required for tuft cell development. C57BL/6J mice infected with RV-A1B on day 6 of life and RV-A2 on day 13 of life showed increased DCLK1+ tuft cells in the large airways. Compared with wild-type mice, RV-infected Pou2f3-/- mice showed reductions in IL-25 mRNA and protein expression, ILC2 expansion, type 2 cytokine expression, mucous metaplasia, lung eosinophils, and airway methacholine responsiveness. We conclude that airway tuft cells are required for the asthma phenotype observed in immature mice undergoing repeated RV infections. Furthermore, RV-induced tuft cell development provides a mechanism by which early-life viral infections could potentiate type 2 inflammatory responses to future infections.
- Published
- 2024
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