TY - JOUR T1 - Imprinting of bronchial epithelial cells upon <em>in vivo</em> rhinovirus infection in asthma patients JF - ERJ Open Research JO - erjor DO - 10.1183/23120541.00522-2021 SP - 00522-2021 AU - Abilash Ravi AU - Saheli Chowdhury AU - Annemiek Dijkhuis AU - Barbara S. Dierdorp AU - Tamara Dekker AU - Rianne Kruize AU - Yanaika S. Sabogal Piñeros AU - Christof J. Majoor AU - Peter J. Sterk AU - René Lutter Y1 - 2021/01/01 UR - http://openres.ersjournals.com/content/early/2021/12/02/23120541.00522-2021.abstract N2 - Background Defective translocation of the translational repressor TIAR (T-cell internal antigen receptor) in bronchial epithelial cells (BECs) from asthma patients underlies epithelial hyperresponsiveness, reflected by an exaggerated production of a select panel of inflammatory cytokines like CXCL-8, IL-6, G-CSF, CXCL-10, upon exposure to TNF and IL-17A. With this study we aimed to clarify whether epithelial hyperresponsiveness is a consistent finding, is changed upon in vivo exposure to rhinovirus-A16 (RV-A16) and, also applies to the bronchoconstrictor endothelin-1.Methods BECs were obtained from asthma patients (n=18) and healthy individuals (n=11), 1 day before and 6 days post RV-A16 exposure. BECs were cultured and stimulated with TNF and IL-17A and inflammatory mediators were analysed. The bronchoalveolar lavage fluid (BALF) was obtained in parallel with BECs to correlate differential cell counts and inflammatory mediators with epithelial hyperresponsiveness.Results Epithelial hyperresponsiveness was confirmed in sequential samples and even increased in BECs from asthma patients after RV-A16 exposure, but not in BECs from healthy individuals. Endothelin-1 tended to increase in BECs from asthma patients collected after RV-A16 exposure, but not in BECs from healthy individuals. In vitro CXCL-8 and endothelin-1 production correlated. In vivo relevance for in vitro CXCL-8 and endothelin-1 production was shown by correlations with FEV1% predicted and CXCL-8 BALF levels.Conclusion Epithelial hyperresponsiveness is an intrinsic defect in BECs from asthma patients, which increases upon viral exposure, but not in BECs from healthy individuals. This epithelial hyperresponsiveness also applies to the bronchoconstrictor endothelin-1, which could be involved in airway obstruction.FootnotesThis manuscript has recently been accepted for publication in the ERJ Open Research. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Please open or download the PDF to view this article.Conflict of interest: Abilash Ravi has nothing to disclose.Conflict of interest: Saheli Chowdhury has nothing to disclose.Conflict of interest: Annemiek Dijkhuis has nothing to disclose.Conflict of interest: Barbara S. Dierdorp has nothing to disclose.Conflict of interest: Tamara Dekker has nothing to disclose.Conflict of interest: Rianne Kruize has nothing to disclose.Conflict of interest: Yanaika S. Sabogal Piñeros has nothing to disclose.Conflict of interest: Christof J. Majoor has nothing to disclose.Conflict of interest: Peter J. Sterk has nothing to disclose.Conflict of interest: Rene Lutter reports support for the present manuscript from the Netherlands Asthma Foundation now Netherlands Lung Fund (grant no: 3-2-07-012; 3.2.10.069) and GlaxoSmithKline (CRT 114696). ER -