{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T11:52:49Z","timestamp":1791373969498,"version":"4.3.1"},"reference-count":149,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"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:p>\n                    Bronchopulmonary dysplasia (BPD), the most common chronic lung disease of prematurity, is at its mechanistic core an immune-developmental disease in which inflammatory injury disrupts normal lung maturation. In the United States, BPD remains among the most common morbidities of very preterm birth, affecting a substantial proportion of infants born before 32 weeks\u2019 gestation. These infants are born before alveolarization is complete, into an inflammatory environment that can impair ongoing lung development. This review advances a single thesis: the heterogeneous prenatal and postnatal insults that precede BPD (chorioamnionitis and the fetal inflammatory response syndrome,\n                    <jats:italic>Ureaplasma<\/jats:italic>\n                    colonization, hyperoxia, mechanical ventilation, sepsis, and intestinal dysbiosis) converge on a small number of innate sensing pathways, principally TLR2 and TLR4 signaling through NF-\u03baB to the NLRP3 inflammasome \u2014 with parallel sterile inputs (mitochondrial reactive oxygen species and additional pattern-recognition receptors) feeding the same inflammasome node. We argue that this convergence is what separates BPD from ordinary neonatal lung injury, and that the outcome depends less on the magnitude of the initiating injurious hits than on failure of the resolution program that should terminate them \u2014 a hypothesis supported by convergent preclinical evidence but not yet established in preterm infants. Evidence is assembled across three domains: the cellular substrate (M1-skewed, classically activated\u2013like alveolar macrophages, NETs, Th17\/Treg imbalance, deficient transplacental IgG transfer); the mediator network (IL-1\u03b2, IL-6, IL-8, TNF-\u03b1, and the loss of endogenous brakes \u2014 specialized pro-resolving mediators, IL-37, Nrf2, short-chain fatty acids); and the signaling architecture (NF-\u03baB, the NLRP3 inflammasome, and trained immunity). We also discuss the mechanistically supported, druggable nodes and the developmental phase in which each is engageable.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1965255","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T11:14:50Z","timestamp":1791371690000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Pathogenesis of bronchopulmonary dysplasia: an immunological perspective"],"prefix":"10.3389","volume":"17","author":[{"given":"David","family":"Riley","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Anne Burnett Marion School of Medicine at Texas Christian University","place":["Fort Worth, TX, United States"]},{"name":"Pediatrix Medical Group of Texas \u2014 Fort Worth Neonatology","place":["Fort Worth, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vineet","family":"Bhandari","sequence":"additional","affiliation":[{"name":"Division of Neonatology, The Children\u2019s Regional Hospital at Cooper, Cooper Medical School of Rowan University","place":["Camden, NJ, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2020-030007","article-title":"Severity of bronchopulmonary dysplasia among very preterm infants in the United States","volume":"148","author":"Jensen","year":"2021","journal-title":"Pediatrics"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1155\/mi\/9480568","article-title":"The inflammatory nexus of bronchopulmonary dysplasia: From molecular pathways to precision therapeutics","volume":"2026","author":"Wang","year":"2026","journal-title":"Mediators Inflammation"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1111\/pan.14365","article-title":"Bronchopulmonary dysplasia","volume":"32","author":"Schmidt","year":"2022","journal-title":"Paediatr Anaesth"},{"key":"B4","doi-asserted-by":"publisher","first-page":"8977","DOI":"10.1038\/ncomms9977","article-title":"The NLRP3 inflammasome is critically involved in the development of bronchopulmonary dysplasia","volume":"6","author":"Liao","year":"2015","journal-title":"Nat Commun"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1093\/ajrcmb\/aanag025","article-title":"CD44 is critical for TLR4-mediated NLRP3 inflammasome activation and the development of bronchopulmonary dysplasia","volume":"74","author":"Liao","year":"2026","journal-title":"Am J Respir Cell Mol Biol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/nm1315","article-title":"Regulation of lung injury and repair by Toll-like receptors and hyaluronan","volume":"11","author":"Jiang","year":"2005","journal-title":"Nat Med"},{"key":"B7","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1038\/sj.cr.7310085","article-title":"The role of Toll-like receptors in non-infectious lung injury","volume":"16","author":"Jiang","year":"2006","journal-title":"Cell Res"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioteChadv.2025.108682","article-title":"Specialized pro-resolving mediators: Biosynthetic pathways, biocatalytic synthesis, and applications","volume":"84","author":"Lee","year":"2025","journal-title":"Biotechnol Adv"},{"key":"B9","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1146\/annurev-physiol-020924-033209","article-title":"Proresolving lipid mediators in the respiratory system","volume":"87","author":"Serhan","year":"2025","journal-title":"Annu Rev Physiol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201812-2348OC","article-title":"The diagnosis of bronchopulmonary dysplasia in very preterm infants. 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