{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T13:48:24Z","timestamp":1792072104560,"version":"4.4.0"},"reference-count":0,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"Abstract<\/jats:title>\n \n Introduction<\/jats:title>\n Heat-not-burn (HNB) tobacco products generate aerosol by heating tobacco and are often perceived as less harmful than conventional cigarettes. However, their effects on human dendritic cells remain poorly understood.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Human monocyte-derived dendritic cells (moDCs) from three independent donors were exposed to HNB extract (HNBE) in immature or LPS-matured states. Surface phenotype, cytokine secretion, redox status, and transcriptomic responses were assessed. Selected RNA-seq findings were independently validated by RT-qPCR using moDCs from three additional independent donors.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n HNBE did not significantly alter DC-SIGN, HLA-DR, CD80, or CD86 expression. In LPS-matured moDCs, 30% HNBE increased IL-6 by approximately 1.3-fold and TNF-\u03b1 by approximately 1.4-fold, whereas other measured cytokines remained unchanged. This preferential response may reflect the primed inflammatory state associated with LPS-induced maturation. HNBE also increased intracellular reactive oxygen species (ROS) and shifted cellular redox balance toward a more oxidized state. RNA sequencing identified 73 differentially expressed genes, including 28 upregulated and 45 downregulated genes, with enrichment of pathways related to immune signaling, antigen processing and presentation, and ribosomal processes. Key transcriptional changes, including those in THBS1, TIMP1, TREM1, and S100A9, were independently validated by RT-qPCR in an additional donor cohort.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n HNBE selectively enhanced IL-6 and TNF-\u03b1 secretion and disrupted redox homeostasis in LPS-matured human moDCs without substantially altering their surface-marker phenotype. These biological changes were accompanied by coordinated HNBE-associated transcriptional alterations, supporting further mechanistic and in vivo investigation of HNB-related immune effects.<\/jats:p>\n <\/jats:sec>\n \n Implication<\/jats:title>\n This study provides human cell-based evidence that HNBE exposure can selectively enhance inflammatory responses and disrupt redox homeostasis in activated dendritic cells, accompanied by coordinated transcriptional alterations in immune-related pathways. These findings broaden current understanding of the immunological and redox effects of HNB products. Although further mechanistic and in vivo validation is required, the results highlight the importance of evaluating potential immune-related health effects when assessing the biological impact of HNB use.<\/jats:p>\n <\/jats:sec>","DOI":"10.1093\/ntr\/ntag225","type":"journal-article","created":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:46:29Z","timestamp":1791978389000},"source":"Crossref","is-referenced-by-count":0,"title":["Heat-not-burn tobacco products induce pro-inflammatory cytokines and oxidative stress, and alter gene expression in human dendritic cells"],"prefix":"10.1093","author":[{"given":"Yu-Chi","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Medical Laboratory, Kaohsiung Armed Forces General Hospital , Kaohsiung ,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Wei","family":"Lin","sequence":"additional","affiliation":[{"name":"Post Baccalaureate Medicine, College of Medicine, Kaohsiung Medical University , Kaohsiung ,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Lun","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Medicine, College of Medicine, Fu Jen Catholic University , New Taipei ,","place":["Taiwan"]},{"name":"Department of Critical Care Medicine, Fu Jen Catholic University Hospital, Fu Jen Catholic University , New Taipei ,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Po-Len","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University , Kaohsiung ,","place":["Taiwan"]},{"name":"Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University , Kaohsiung ,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsiao-Hsuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, College of Medicine, National Cheng Kung University , Tainan ,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sin-Hua","family":"Moi","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University , Kaohsiung ,","place":["Taiwan"]},{"name":"Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University , Kaohsiung ,","place":["Taiwan"]},{"name":"Faculty of Medicine, College of Medicine, Kaohsiung Medical University , Kaohsiung ,","place":["Taiwan"]},{"name":"Center of Applied Genomics, Kaohsiung Medical University , Kaohsiung ,","place":["Taiwan"]},{"name":"Research Center for Precision Environmental Medicine, Kaohsiung Medical University , Kaohsiung ,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsiu-Lin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University , Kaohsiung ,","place":["Taiwan"]},{"name":"Department of Pediatrics, Kaohsiung Medical University Hospital , Kaohsiung ,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6377-4332","authenticated-orcid":false,"given":"I-Ling","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University , Kaohsiung ,","place":["Taiwan"]},{"name":"Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University , Kaohsiung ,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,10,15]]},"container-title":["Nicotine & Tobacco Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ntr\/advance-article-pdf\/doi\/10.1093\/ntr\/ntag225\/71966146\/ntag225.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ntr\/advance-article-pdf\/doi\/10.1093\/ntr\/ntag225\/71966146\/ntag225.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T13:12:36Z","timestamp":1792069956000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ntr\/advance-article\/doi\/10.1093\/ntr\/ntag225\/8917347"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,15]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1093\/ntr\/ntag225","relation":{},"ISSN":["1469-994X"],"issn-type":[{"value":"1469-994X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,15]]},"article-number":"ntag225"}}