{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T09:23:25Z","timestamp":1783329805629,"version":"3.54.6"},"reference-count":27,"publisher":"European Respiratory Society (ERS)","issue":"4","license":[{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["ERJ Open Res"],"accepted":{"date-parts":[[2025,12,4]]},"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>\n                      Activation of the angiotensin II type 2 receptor (AT\n                      <jats:sub>2<\/jats:sub>\n                      receptor; encoded by\n                      <jats:italic>AGTR2<\/jats:italic>\n                      ) has been shown to be beneficial during tissue injury and repair. Therefore, we aimed to investigate the expression of AT\n                      <jats:sub>2<\/jats:sub>\n                      receptor in human alveolar type II (ATII) cells, a cell population responsible for lung repair and regeneration, and the effect of the AT\n                      <jats:sub>2<\/jats:sub>\n                      receptor agonist buloxibutid (also known as C21), in an\n                      <jats:italic>in vitro<\/jats:italic>\n                      model of viral infection using primary ATII cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We described the expression of AT\n                      <jats:sub>2<\/jats:sub>\n                      receptor messenger RNA using publicly available lung single-cell RNA sequencing datasets. We evaluated the effects of buloxibutid on ATII cell biology at baseline and in response to treatment with double-stranded RNA (polyinosinic:polycytidylic acid, a pathogen associated molecular pattern) using MTS cytotoxicity assay, transcriptomic analysis and ELISA.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We found that buloxibutid was well tolerated by ATII cells under all conditions tested. RNA sequencing demonstrated that ATII cells responded to polyinosinic:polycytidylic acid with induction of a characteristic antiviral innate immune response. Gene set enrichment analysis revealed that buloxibutid caused a significant suppression of polyinosinic:polycytidylic acid-induced proinflammatory responses, whereas it was without effect on the expression of antiviral genes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings suggest that buloxibutid may have therapeutic potential for treatment of respiratory viral pneumonias by limiting excessive proinflammatory responses that have the potential to lead to a cytokine storm, while maintaining a protective antiviral response.<\/jats:p>\n                  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