Injury-induced pulmonary tuft cells are heterogenous, arise independent of key Type 2 cytokines, and are dispensable for dysplastic repair
Year: 2022
Type: article
Abstract: While the lung bears significant regenerative capacity, severe viral pneumonia can chronically impair lung function by triggering dysplastic remodeling. The connection between these enduring changes and chronic disease remains poorly understood. We recently described the emergence of tuft cells within Krt5 + dysplastic regions after influenza injury. Using bulk and single cell transcriptomics, we characterized and delineated multiple distinct tuft cell populations that arise following influenza clearance. Distinct from intestinal tuft cells which rely on Type 2 immune signals for their expansion, neither IL-25 nor IL-4Rα signaling are required to drive tuft cell development in dysplastic/injured lungs. Furthermore, tuft cells were also observed upon bleomycin injury, suggesting that their development may be a general response to severe lung injury. While intestinal tuft cells promote growth and differentiation of surrounding epithelial cells, in the lungs of tuft cell deficient mice, Krt5 + dysplasia still occurs, goblet cell production is unchanged, and there remains no appreciable contribution of Krt5 + cells into more regionally appropriate alveolar Type 2 cells. Together, these findings highlight unexpected differences in signals necessary for lung tuft cell amplification and establish a framework for future elucidation of tuft cell functions in pulmonary health and disease.
Source: eLife
DOI: 10.7554/elife.78074
Language: English
Topic: IL-33, ST2, and ILC Pathways
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,500
Funders: U.S. Department of Veterans Affairs, A.P. Giannini Foundation, Giannini Foundation of Agricultural Economics, Lisa Dean Moseley Foundation, National Institutes of Health, University of California, San Diego, University of California, San Francisco, Fonds de Recherche du Québec - Santé, National Heart, Lung, and Blood Institute, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, National Center for Complementary and Integrative Health, School of Medicine, University of California, San Diego
Awards: G1966189233, G2041273731, Solitary chemosensory / tuft cells in lung regeneration and inflammation, G3033040839, G3350646238, G3949373414, G4366002869, Genetic Basis of Normal and Pathological Alveologenesis in Lung Development, University of California San Diego Neuroscience Microscopy Imaging Core, G639426234, Not all those who wander are lost: Specification of lung innervating sensory neurons, G6753346425, Role of ILC2s in lung maintenance and repair, G7719232382, G8191216718, G8761015740, G9000255603, G9000307058, University of Pennsylvania Diabetes Research Center, Pathways in Biological Sciences Training Program, Multidisciplinary Training Program in Lung Disease
OpenAlex ID: W4294991033