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The endothelin system has been linked to asthma, but the impact of ET\n                      <jats:sub>B<\/jats:sub>\n                      receptor deficiency on allergic airway inflammation remains uncharted. This study explores how the endothelin system influences allergic airway inflammation and hyperresponsiveness.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We used rescued ET\n                      <jats:sub>B<\/jats:sub>\n                      receptor-deficient (ET\n                      <jats:sub>B<\/jats:sub>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      ) mice to obviate lethal inherited Hirschsprung disease, prepro-ET-1 overexpressing (\n                      <jats:sub>pre<\/jats:sub>\n                      ET\n                      <jats:sup>tg<\/jats:sup>\n                      ), and wild-type (WT) mice. Basal airway resistance and responsiveness to broncho-constrictive stimuli were assessed in isolated, perfused and ventilated lungs of na\u00efve mice. Additionally, we analysed the humoral immune response and airway hyperresponsiveness following induction of type 2 airway inflammation induced by systemic ovalbumin (OVA) sensitisation and repeated airway challenge with aerosolised OVA.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Na\u00efve ET\n                      <jats:sub>B<\/jats:sub>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice exhibited significantly heightened airway responsiveness compared to na\u00efve WT mice. After OVA sensitisation and challenge, ET\n                      <jats:sub>B<\/jats:sub>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice displayed increased OVA-specific immunoglobulin E levels, intensified allergic airway inflammation and hyperresponsiveness compared to WT mice. Conversely,\n                      <jats:sub>pre<\/jats:sub>\n                      ET\n                      <jats:sup>tg<\/jats:sup>\n                      mice displayed reduced immunoglobulin E levels, airway inflammation and hyperresponsiveness.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our findings suggest ET\n                      <jats:sub>B<\/jats:sub>\n                      receptors have a protective role in asthma-associated allergic airway inflammation and hyperresponsiveness. The increased asthma phenotype in sensitised and challenged ET\n                      <jats:sub>B<\/jats:sub>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice is attributed to ET\n                      <jats:sub>B<\/jats:sub>\n                      -specific immunomodulatory mechanisms, rather than to elevated levels of ET-1 resulting from impaired ET\n                      <jats:sub>B<\/jats:sub>\n                      -mediated ET-1 clearance. This conclusion is supported by the diminished asthma-phenotype observed in sensitised and challenged\n                      <jats:sub>pre<\/jats:sub>\n                      ET\n                      <jats:sup>tg<\/jats:sup>\n                      mice. Therefore, adjusting endothelin signalling could offer a promising approach to managing asthma.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1183\/23120541.00489-2025","type":"journal-article","created":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T14:10:14Z","timestamp":1755785414000},"page":"00489-2025","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["ET\n                    <sub>B<\/sub>\n                    receptor deficiency amplifies allergic airway inflammation and hyperresponsiveness"],"prefix":"10.1183","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9189-4318","authenticated-orcid":false,"given":"Christoph","family":"Tabeling","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carla R.","family":"Gonz\u00e1lez 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