{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T22:36:45Z","timestamp":1791412605923,"version":"4.3.3"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T00:00:00Z","timestamp":1743638400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T00:00:00Z","timestamp":1743638400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pediatr Res"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Bronchopulmonary dysplasia (BPD) is a complex disease involving aberrant immune responses across the lifespan, but these mechanisms are challenging to follow in human infants. Leveraging novel Signatures of Macrophage Reactivity and Tolerance (SMaRT), we hypothesized that distinct profiles of immune cell polarization in blood and lung are associated with BPD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Published transcriptomic datasets of cord blood-derived monocytes (CB-MNC), peripheral blood monocytes (PBMC) and tracheal aspirate-derived lung macrophages were linked to placental inflammatory (PID) and vascular (PVD) disease states using Amsterdam criteria, and BPD outcomes using NIH consensus criteria. Datasets were integrated using SMaRT to investigate monocyte-macrophage polarization tracked over the neonatal course.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      At birth and day 1 (D1), CB-MNCs and lung macrophages exhibited significant reactivity with PID versus PVD. After D14, macrophages from PID versus PVD-exposed infants exhibited reactive phenotypes (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.002), with convergence towards original placental disease. Macrophages exhibited reactivity with BPD on D1-D7 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.007), but no difference after D14. At birth, CB-MNCs from BPD patients exhibited tolerance, which persisted in PBMCs throughout the neonatal period.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Inflammatory versus vascular-mediated processes in developing lungs are influenced by immune cells programmed by distinct placental disease states. Circulating monocytes may play a role in attenuating macrophage reactivity towards a tolerant phenotype.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Impact<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Bronchopulmonary dysplasia is a complex, multifactorial chronic lung disease in which the mechanisms of placenta-lung crosstalk are poorly understood.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>This study uses novel AI approaches to understand how fetal monocytes and lung macrophages contribute to the pathogenesis of BPD.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The study identified changes in macrophage reactivity versus tolerance that could explain the heterogeneity and adaptability of immune cells and the placenta in modulating health and disease in the developing fetus and neonate.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s41390-025-04025-w","type":"journal-article","created":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T16:09:28Z","timestamp":1743782968000},"page":"2352-2362","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Bronchopulmonary dysplasia: signatures of monocyte-macrophage reactivity and tolerance define novel placenta-lung endotypes"],"prefix":"10.1038","volume":"98","author":[{"given":"Karen K.","family":"Mestan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhineet M.","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Lazar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonalisa","family":"Pandey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mana M.","family":"Parast","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise C.","family":"Laurent","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence S.","family":"Prince","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debashis","family":"Sahoo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,3]]},"reference":[{"key":"4025_CR1","doi-asserted-by":"publisher","first-page":"1026954","DOI":"10.3389\/fimmu.2022.1026954","volume":"13","author":"C Kerneur","year":"2022","unstructured":"Kerneur, C., Cano, C. 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