{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:16:27Z","timestamp":1787008587829,"version":"build-2736575974"},"reference-count":63,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T00:00:00Z","timestamp":1719273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"JSPS KAKENHI","award":["JP20K17286"],"award-info":[{"award-number":["JP20K17286"]}]},{"name":"JSPS KAKENHI","award":["JP19K08867"],"award-info":[{"award-number":["JP19K08867"]}]},{"name":"JSPS KAKENHI","award":["JP23K07334"],"award-info":[{"award-number":["JP23K07334"]}]},{"name":"JSPS KAKENHI","award":["JP22H03043"],"award-info":[{"award-number":["JP22H03043"]}]},{"name":"JSPS KAKENHI","award":["JP22ek0109481h0003"],"award-info":[{"award-number":["JP22ek0109481h0003"]}]},{"name":"JSPS KAKENHI","award":["JP20ek0109411"],"award-info":[{"award-number":["JP20ek0109411"]}]},{"name":"JSPS KAKENHI","award":["JP20wm0325002h"],"award-info":[{"award-number":["JP20wm0325002h"]}]},{"name":"JSPS KAKENHI","award":["JP22FC1004"],"award-info":[{"award-number":["JP22FC1004"]}]},{"name":"JSPS KAKENHI","award":["JP20FC1054"],"award-info":[{"award-number":["JP20FC1054"]}]},{"name":"JSPS KAKENHI","award":["JP21FC1005"],"award-info":[{"award-number":["JP21FC1005"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,8,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The clinical spectrum of Down syndrome (DS) ranges from congenital malformations to premature aging and early-onset senescence. Excessive immunoreactivity and oxidative stress are thought to accelerate the pace of aging in DS patients; however, the immunological profile remains elusive. We investigated whether peripheral blood monocyte-derived dendritic cells (MoDCs) in DS patients respond to lipopolysaccharide (LPS) distinctly from non-DS control MoDCs. Eighteen DS patients (age 2\u201347 years, 12 males) and 22 controls (age 4\u201340 years, 15 males) were enrolled. CD14-positive monocytes were immunopurified and cultured for 7 days in the presence of granulocyte-macrophage colony-stimulating factor and IL-4, yielding MoDCs in vitro. After the LPS-stimulation for 48 hours from days 7 to 9, culture supernatant cytokines were measured by multiplex cytokine bead assays, and bulk-prepared RNA from the cells was used for transcriptomic analyses. MoDCs from DS patients produced cytokines\/chemokines (IL-6, IL-8, TNF-\u03b1, MCP-1, and IP-10) at significantly higher levels than those from controls in response to LPS. RNA sequencing revealed that DS-derived MoDCs differentially expressed 137 genes (74 upregulated and 63 downregulated) compared with controls. A gene enrichment analysis identified 5 genes associated with Toll-like receptor signaling (KEGG: hsa04620, P\u2005=\u20050.00731) and oxidative phosphorylation (hsa00190, P\u2005=\u20050.0173) pathways. MoDCs obtained from DS patients showed higher cytokine or chemokine responses to LPS than did control MoDCs. Gene expression profiles suggest that hyperactive Toll-like receptor and mitochondrial oxidative phosphorylation pathways configure the immunoreactive signature of MoDCs in DS patients.<\/jats:p>","DOI":"10.1093\/cei\/uxae048","type":"journal-article","created":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T11:30:53Z","timestamp":1719228653000},"page":"291-299","source":"Crossref","is-referenced-by-count":2,"title":["The immunoreactive signature of monocyte-derived dendritic cells from patients with Down syndrome"],"prefix":"10.1093","volume":"217","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4633-110X","authenticated-orcid":false,"given":"Kentaro","family":"Nakashima","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University , Fukuoka , Japan"},{"name":"Department of Pediatrics, University of Occupational and Environmental Health , Kitakyushu , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Imai","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University , Fukuoka , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Shiraishi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University , Fukuoka , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryoko","family":"Unose","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University , Fukuoka , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hironori","family":"Goto","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University , Fukuoka , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8863-5737","authenticated-orcid":false,"given":"Yusaku","family":"Nagatomo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University , Fukuoka , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanako","family":"Kojima-Ishii","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University , Fukuoka , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichi","family":"Mushimoto","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University , Fukuoka , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kei","family":"Nishiyama","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University , Fukuoka , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichiro","family":"Yamamura","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University , Fukuoka , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hazumu","family":"Nagata","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University , Fukuoka , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masataka","family":"Ishimura","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University , Fukuoka , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Kusuhara","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Occupational and Environmental Health , Kitakyushu , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0056-9988","authenticated-orcid":false,"given":"Yuhki","family":"Koga","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University , Fukuoka , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5747-8692","authenticated-orcid":false,"given":"Yasunari","family":"Sakai","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University , Fukuoka , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shouichi","family":"Ohga","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University , Fukuoka , 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