{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T12:17:04Z","timestamp":1789042624098,"version":"build-2803163510"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Surfactant protein (SP-D) is an anti-inflammatory host defense molecule, produced by epithelial cells and present on mucosal surfaces throughout the human and mouse body. In the present study, we investigated whether SP-D attenuates chemotherapy-induced gastrointestinal toxicity and inflammation in mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      SP-D knockout (KO,\n                      <jats:italic>Sftpd<\/jats:italic>\n                      <jats:sup>-\/-<\/jats:sup>\n                      ) mice and wild type (WT,\n                      <jats:italic>Sftpd<\/jats:italic>\n                      <jats:sup>+\/+<\/jats:sup>\n                      ) littermates were treated with doxorubicin (20mg\/kg) or saline and sacrificed at day 3 o rat day 7, post-administration. Gastrointestinal toxicity was evaluated by weight change, citrulline levels, and histopathology. Genetic expression of genes related to chemotherapy-induced mucositis, inflammation, apoptosis, and repair of the damaged epithelium was investigated by reverse transcription quantitative polymerase chain reaction (RT-qPCR) on jejunal and colonic samples.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Doxorubicin significantly reduced bodyweight, and KO mice lost significantly more weight relative to WT mice. Transcriptional analyses showed a significant SP-D-dependent increase of gasdermin genes (\n                      <jats:italic>Gsdmc2\/3<\/jats:italic>\n                      and\n                      <jats:italic>Gsdmc4<\/jats:italic>\n                      ) in the small intestine. The doxorubicin challenge did not alter intestinal SP-D expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>In conclusion, SP-D had a limited but significant impact on mouse gastrointestinal toxicity after chemotherapy-induced mucositis, which primarily involved weight loss of unknown cause and had no or limited effects on intestinal morphology and inflammation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1913868","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T11:53:56Z","timestamp":1789041236000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Limited effect of surfactant protein D ablation on doxorubicin-induced intestinal toxicity in 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