{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T12:00:07Z","timestamp":1764158407454,"version":"3.46.0"},"reference-count":59,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH\/NHLBI Office of The Director, National Institutes of Health","award":["R01HL155104","NIH\/NHLBI R21HL165411","NIH\/NHLBI R01HL141856","NIH\/NICHD R24HD000836"],"award-info":[{"award-number":["R01HL155104","NIH\/NHLBI R21HL165411","NIH\/NHLBI R01HL141856","NIH\/NICHD R24HD000836"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Respiratory tract infections (RTIs) are amongst the leading causes of hospitalizations in children with Down syndrome (DS). Their elevated susceptibility likely stems from structural differences in the airways and immune system abnormalities. The aim of this study was to characterize immune cells in prenatal Trisomy 21 (T21) lungs, potentially explaining vulnerability to RTIs. Single-cell RNA sequencing was used to profile immune cells in prenatal T21 (n = 5) and non-T21 (n = 4) prenatal lungs. Spatial phenotypes were assessed via fluorescent in situ hybridization and immunofluorescent staining on prenatal lung tissue sections. Gene expression analysis was also performed on isolated immune cells from lung single-cell suspensions. Several major immune cell populations were identified. A total of 84 DEGs were identified in at least 1 of the 14 different clusters. A significant decrease in the percentage of B cells was observed in T21 lungs (FDR = 0.0037, * p &lt; 0.05). Furthermore, qRT-PCR demonstrated B cell markers were significantly decreased in T21, including those associated with B cell maturation (* p &lt; 0.05 and ** p &lt; 0.01). Several of these markers were also decreased at the protein level (i.e., CD20 and CD38; * p &lt; 0.05 and ** p &lt; 0.01). Our data demonstrate changes in the T21 pulmonary immune system in utero, primarily within the B cell population, which may contribute to the increased susceptibility to RTIs observed in children with DS.<\/jats:p>","DOI":"10.3390\/cells14231866","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T11:43:22Z","timestamp":1764157402000},"page":"1866","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Alterations in Resident Immune Cells in Prenatal Trisomy 21 Lungs"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-2986-0103","authenticated-orcid":false,"given":"Andrew","family":"Frauenpreis","sequence":"first","affiliation":[{"name":"Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA 90502, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1140-7845","authenticated-orcid":false,"given":"Soumyaroop","family":"Bhattacharya","sequence":"additional","affiliation":[{"name":"Center for Children\u2019s Health Research, University of Rochester Medical Center, Rochester, NY 14642, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Randa","family":"Belgacemi","sequence":"additional","affiliation":[{"name":"Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA 90502, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pauline","family":"Sokolskiy","sequence":"additional","affiliation":[{"name":"Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA 90502, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gail","family":"Deutsch","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Seattle Children\u2019s Research Institute, Seattle, WA 98101, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4342-1839","authenticated-orcid":false,"given":"Nicholas","family":"Jendzjowsky","sequence":"additional","affiliation":[{"name":"Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA 90502, USA"},{"name":"David Geffen School of Medicine at University of California-Los Angeles, Los Angeles, CA 90095, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6762-8407","authenticated-orcid":false,"given":"Ian A.","family":"Glass","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Washington School of Medicine, Seattle, WA 98195, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas J.","family":"Mariani","sequence":"additional","affiliation":[{"name":"Center for Children\u2019s Health Research, University of Rochester Medical Center, Rochester, NY 14642, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3148-7352","authenticated-orcid":false,"given":"Denise","family":"Al Alam","sequence":"additional","affiliation":[{"name":"Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA 90502, USA"},{"name":"David Geffen School of Medicine at University of California-Los Angeles, Los Angeles, CA 90095, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soula","family":"Danopoulos","sequence":"additional","affiliation":[{"name":"Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA 90502, USA"},{"name":"David Geffen School of Medicine at University of California-Los Angeles, Los Angeles, CA 90095, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5473","DOI":"10.1038\/s41467-024-49781-1","article-title":"Variegated overexpression of chromosome 21 genes reveals molecular and immune subtypes of Down syndrome","volume":"15","author":"Donovan","year":"2024","journal-title":"Nat. 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