Club Cell TRPV4 Serves as a Damage Sensor Driving Lung Allergic Inflammation

Darin L. Wiesner; Richard M. Merkhofer; Carole Ober; Gregory C. Kujoth; Mengyao Niu; Nancy P. Keller; James E. Gern; Rebecca A. Brockman-Schneider; Michael D. Evans; Daniel J. Jackson; Thomas Warner; Nizar N. Jarjour; Stephane J. Esnault; Michael B. Feldman; Matthew Freeman; Hongmei Mou; Jatin M. Vyas; Bruce S. Klein

doi:10.1016/j.chom.2020.02.006

Club Cell TRPV4 Serves as a Damage Sensor Driving Lung Allergic Inflammation

Darin L. Wiesner, Richard M. Merkhofer, Carole Ober, Gregory C. Kujoth, Mengyao Niu, Nancy P. Keller, James E. Gern, Rebecca A. Brockman-Schneider, Michael D. Evans, Daniel J. Jackson, Thomas Warner, Nizar N. Jarjour, Stephane J. Esnault, Michael B. Feldman, Matthew Freeman, Hongmei Mou, Jatin M. Vyas, Bruce S. Klein

CTSI Biostatistics

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44 Scopus citations

Abstract

Airway epithelium is the first body surface to contact inhaled irritants and report danger. Here, we report how epithelial cells recognize and respond to aeroallergen alkaline protease 1 (Alp1) of Aspergillus sp., because proteases are critical components of many allergens that provoke asthma. In a murine model, Alp1 elicits helper T (Th) cell-dependent lung eosinophilia that is initiated by the rapid response of bronchiolar club cells to Alp1. Alp1 damages bronchiolar cell junctions, which triggers a calcium flux signaled through calcineurin within club cells of the bronchioles, inciting inflammation. In two human cohorts, we link fungal sensitization and/or asthma with SNP/protein expression of the mechanosensitive calcium channel, TRPV4. TRPV4 is also necessary and sufficient for club cells to sensitize mice to Alp1. Thus, club cells detect junction damage as mechanical stress, which signals danger via TRPV4, calcium, and calcineurin to initiate allergic sensitization.

Original language	English (US)
Pages (from-to)	614-628.e6
Journal	Cell Host and Microbe
Volume	27
Issue number	4
DOIs	https://doi.org/10.1016/j.chom.2020.02.006
State	Published - Apr 8 2020

Bibliographical note

Publisher Copyright:
© 2020 Elsevier Inc.

Keywords

Aspergillus
TRPV4
alkaline protease 1
asthma
calcineurin
calcium
club cells

UN SDGs

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Wiesner, D. L., Merkhofer, R. M., Ober, C., Kujoth, G. C., Niu, M., Keller, N. P., Gern, J. E., Brockman-Schneider, R. A., Evans, M. D., Jackson, D. J., Warner, T., Jarjour, N. N., Esnault, S. J., Feldman, M. B., Freeman, M., Mou, H., Vyas, J. M., & Klein, B. S. (2020). Club Cell TRPV4 Serves as a Damage Sensor Driving Lung Allergic Inflammation. Cell Host and Microbe, 27(4), 614-628.e6. https://doi.org/10.1016/j.chom.2020.02.006

Wiesner, DL, Merkhofer, RM, Ober, C, Kujoth, GC, Niu, M, Keller, NP, Gern, JE, Brockman-Schneider, RA, Evans, MD, Jackson, DJ, Warner, T, Jarjour, NN, Esnault, SJ, Feldman, MB, Freeman, M, Mou, H, Vyas, JM & Klein, BS 2020, 'Club Cell TRPV4 Serves as a Damage Sensor Driving Lung Allergic Inflammation', Cell Host and Microbe, vol. 27, no. 4, pp. 614-628.e6. https://doi.org/10.1016/j.chom.2020.02.006

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Club Cell TRPV4 Serves as a Damage Sensor Driving Lung Allergic Inflammation

Abstract

Bibliographical note

Keywords

UN SDGs

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