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

Cell Host & Microbe
Darin L WiesnerBruce S Klein

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.

References

May 12, 2000·American Journal of Respiratory and Critical Care Medicine·J BousquetA M Vignola
Jun 16, 2000·The Journal of Allergy and Clinical Immunology·H F KauffmanP Borger
May 2, 2002·Cell·Gerald R Crabtree, Eric N Olson
Jul 26, 2002·Mediators of Inflammation·Shahida ShahanaGodfried M Roomans
Nov 8, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Scott M DrouinRick A Wetsel
Apr 12, 2003·Pediatric Allergy and Immunology : Official Publication of the European Society of Pediatric Allergy and Immunology·Robert F Lemanske
Apr 15, 2003·The Journal of Biological Chemistry·Makoto SuzukiMasashi Imai
Jan 22, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yutaka NakamuraNizar N Jarjour
Apr 13, 2004·American Journal of Physiology. Lung Cellular and Molecular Physiology·Yanlin JiaJohn A Hey
Nov 6, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Elizabeth C CatesManel Jordana
Nov 13, 2004·The Journal of Allergy and Clinical Immunology·Charles E Reed, Hirohito Kita
Jun 16, 2005·Seminars in Immunology·Beatriz LeónCarlos Ardavín
Jul 9, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kiyono ShiraishiTsutomu Takeuchi
Mar 2, 2006·The European Respiratory Journal·D W DenningR M Niven
Nov 7, 2006·Developmental Cell·Mirna Perez-Moreno, Elaine Fuchs
Feb 15, 2007·Nature Reviews. Molecular Cell Biology·Christopher M Overall, Carl P Blobel
Jun 21, 2007·Annual Review of Biochemistry·Kartik Venkatachalam, Craig Montell
Aug 22, 2007·International Archives of Allergy and Immunology·Birgit Simon-NobbeMichael Breitenbach
Sep 15, 2007·Biochimica Et Biophysica Acta·Andrea Hartsock, W James Nelson
Sep 26, 2007·The Journal of Experimental Medicine·Edward J KerschenHartmut Weiler
Dec 13, 2007·The Journal of Allergy and Clinical Immunology·Stephen T Holgate
May 7, 2008·American Journal of Respiratory Cell and Molecular Biology·Ashwini S SabnisChristopher A Reilly
Jun 21, 2008·American Journal of Respiratory and Critical Care Medicine·Daniel J JacksonRobert F Lemanske
Dec 9, 2008·American Journal of Respiratory and Critical Care Medicine·Paul F MercerRachel C Chambers
Mar 13, 2009·Human Molecular Genetics·Guohua ZhuSreekumar G Pillai
Apr 24, 2009·Proceedings of the American Thoracic Society·Yvonne M W Janssen-HeiningerAlbert van der Vliet
May 16, 2009·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Satish L DeshmaneBassel E Sawaya
Oct 21, 2009·Cell Biochemistry and Biophysics·Jun Yin, Wolfgang M Kuebler
Dec 8, 2009·American Journal of Physiology. Heart and Circulatory Physiology·Suelhem A MendozaDavid X Zhang
Apr 24, 2010·The Journal of Biological Chemistry·Takaaki SokabeMakoto Tominaga
May 14, 2010·Clinical and Vaccine Immunology : CVI·Stanley A Plotkin
May 22, 2010·Journal of Proteome Research·Dev SriranganadaneMichel Monod
Jun 11, 2011·International Journal of Medical Microbiology : IJMM·Dirk WartenbergAxel A Brakhage
Sep 2, 2011·Proceedings of the National Academy of Sciences of the United States of America·Rachel L ZemansGregory P Downey
Jan 31, 2012·The Journal of Allergy and Clinical Immunology·Alan P KnutsenAndrew J Wardlaw
Jun 30, 2012·Nature Methods·Johannes SchindelinAlbert Cardona
Aug 2, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·René M RoyBruce S Klein
Jul 6, 2013·Nature Reviews. Immunology·William C GauseJudith E Allen

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Citations

Jan 3, 2021·Trends in Immunology·Darine W El-NaccacheWilliam C Gause
Feb 19, 2021·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Kai NiLinhong Deng
May 1, 2021·Cells·Suhasini RajanAlexander Dietrich
Jun 3, 2021·Journal of Fungi·Rebecca A WardJatin M Vyas
Jun 4, 2021·Journal of Asthma and Allergy·Andrew J WardlawCatherine H Pashley
Aug 9, 2021·Molecular Aspects of Medicine·Zsolt I KomlósiCezmi A Akdis

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