{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T14:41:53Z","timestamp":1777041713783,"version":"3.51.4"},"reference-count":70,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T00:00:00Z","timestamp":1763769600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32170497"],"award-info":[{"award-number":["32170497"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32261160571"],"award-info":[{"award-number":["32261160571"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006606","name":"Tianjin Natural Science Foundation","doi-asserted-by":"publisher","award":["22JCZXJC00090"],"award-info":[{"award-number":["22JCZXJC00090"]}],"id":[{"id":"10.13039\/501100006606","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Tianjin Science and Technology Major Project","award":["24ZXZSSS00490"],"award-info":[{"award-number":["24ZXZSSS00490"]}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004945","name":"Nankai University","doi-asserted-by":"publisher","award":["63223026"],"award-info":[{"award-number":["63223026"]}],"id":[{"id":"10.13039\/501100004945","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004945","name":"Nankai University","doi-asserted-by":"publisher","award":["63233045"],"award-info":[{"award-number":["63233045"]}],"id":[{"id":"10.13039\/501100004945","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004945","name":"Nankai University","doi-asserted-by":"publisher","award":["63241536"],"award-info":[{"award-number":["63241536"]}],"id":[{"id":"10.13039\/501100004945","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Special Research Fund for Central Universities, Peking Union Medical College","award":["3332023020"],"award-info":[{"award-number":["3332023020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Lymphatic malformations (LMs) are debilitating and potentially life-threatening diseases. However, the immune phenotype of circulating cells and underlying molecular mechanisms in LMs remain poorly understood. Here, we performed integrated single-cell RNA, T-cell receptor, and B-cell receptor sequencing (scRNA-seq, scTCR-seq, and scBCR-seq) of peripheral blood and pleural effusion from patients with LMs to delineate their immune landscape. We identified an expansion of pro-inflammatory CD14+CD16+ monocytes and atypical memory B cells, accompanied by reduced cytotoxic CD8+ T and natural killer (NK) cells. Functional analysis revealed impaired antigen processing and presentation in CD14+ monocytes, and dysregulated transcription factor activity, potentially driving immune dysfunction. Additionally, LMs exhibited substantial remodeling of TCR and BCR repertoires, with shifts in clonality and diversity. Moreover, the CXCL16\u2013CXCR6 interaction was associated with inflammatory responses, while upregulation of the inhibitory checkpoint HLA-E: CD94-NKG2A potentially contributed to impaired NK cell activity. Finally, we constructed a shared pro-inflammatory monocyte program and revealed S100A8 as a potential therapeutic target for LMs. We further demonstrated that S100A8 pharmacological inhibition could ameliorate the pathological phenotype of LMs. Collectively, our findings delineate cell type-specific immune dysregulation in LMs, offering insights for therapeutic development.<\/jats:p>","DOI":"10.1093\/procel\/pwaf103","type":"journal-article","created":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T13:04:11Z","timestamp":1763643851000},"page":"320-338","source":"Crossref","is-referenced-by-count":0,"title":["Multidimensional single-cell analysis reveals immune dysfunction and inflammatory response in lymphatic malformations"],"prefix":"10.1093","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-8463-9301","authenticated-orcid":false,"given":"Chunxiao","family":"Chen","sequence":"first","affiliation":[{"name":"Vascular Anomalies and Vascular Interventional Center, Capital Center for Children\u2019s Health, Capital Medical University, Capital Institute of Pediatrics , Beijing 100020,","place":["China"]},{"name":"State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai University , Tianjin 300071,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4361-0522","authenticated-orcid":false,"given":"Wenhao","family":"Ju","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiovascular Disease, Department of Structural Heart Disease, National Center for Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Key Laboratory of Innovative Cardiovascular Devices, Chinese Academy of Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 100037,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1471-7948","authenticated-orcid":false,"given":"Xueying","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai University , Tianjin 300071,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9503-8003","authenticated-orcid":false,"given":"Kexin","family":"Yao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai University , Tianjin 300071,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0211-9227","authenticated-orcid":false,"given":"Jun","family":"Cao","sequence":"additional","affiliation":[{"name":"College of Chemistry and Life Science, Beijing University of Technology , Beijing 100124,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0822-5883","authenticated-orcid":false,"given":"Songqi","family":"Duan","sequence":"additional","affiliation":[{"name":"College of Food Science, Sichuan Agricultural University , Ya\u2019an 625014,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1739-5806","authenticated-orcid":false,"given":"Xueqi","family":"Lv","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai University , Tianjin 300071,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9593-6535","authenticated-orcid":false,"given":"Tianli","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai University , Tianjin 300071,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7842-9146","authenticated-orcid":false,"given":"Sanlin","family":"Li","sequence":"additional","affiliation":[{"name":"Vascular Anomalies and Vascular Interventional Center, Capital Center for Children\u2019s Health, Capital Medical University, Capital Institute of Pediatrics , Beijing 100020,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3397-2888","authenticated-orcid":false,"given":"Jiawen","family":"Li","sequence":"additional","affiliation":[{"name":"Vascular Anomalies and Vascular Interventional Center, Capital Center for Children\u2019s Health, Capital Medical University, Capital Institute of Pediatrics , Beijing 100020,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5692-5561","authenticated-orcid":false,"given":"Feng","family":"He","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunology, Capital Center for Children\u2019s Health, Capital Medical University, Capital Institute of Pediatrics , Beijing 100020,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8221-1279","authenticated-orcid":false,"given":"Baofa","family":"Sun","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, College of Life Sciences, Nankai University , Tianjin 300071,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3318-215X","authenticated-orcid":false,"given":"Gang","family":"Shen","sequence":"additional","affiliation":[{"name":"Vascular Anomalies and Vascular Interventional Center, Capital Center for Children\u2019s Health, Capital Medical University, Capital Institute of Pediatrics , Beijing 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regulate the entrance of B lymphocytes into lymph nodes and B cell motility within lymph node follicles","volume":"22","author":"Han","year":"2005","journal-title":"Immunity"},{"key":"2026042408413339400_pwaf103-B26","article-title":"Plasma proteomics identifies S100A8\/A9 as a novel biomarker and therapeutic target for fulminant myocarditis","author":"He","year":"2025","journal-title":"J Adv Res"},{"key":"2026042408413339400_pwaf103-B27","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1038\/nri2154","article-title":"Developmental pathways that generate natural-killer-cell diversity in mice and humans","volume":"7","author":"Huntington","year":"2007","journal-title":"Nat Rev Immunol"},{"key":"2026042408413339400_pwaf103-B28","doi-asserted-by":"crossref","first-page":"e12776","DOI":"10.1371\/journal.pone.0012776","article-title":"Inferring regulatory networks from expression data using tree-based methods","volume":"5","author":"Huynh-Thu","year":"2010","journal-title":"PLoS 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