{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:49:32Z","timestamp":1791218972660,"version":"4.1.0"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2013,7,1]],"date-time":"2013-07-01T00:00:00Z","timestamp":1372636800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Beijing Municipal Committee for Science and Technology","award":["Z121100005212004"],"award-info":[{"award-number":["Z121100005212004"]}]},{"DOI":"10.13039\/501100012166","name":"National Basic Research Program of China","doi-asserted-by":"crossref","award":["2010CB944801"],"award-info":[{"award-number":["2010CB944801"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Academic Human Resources Development in Institutions of Higher Learning Under the Jurisdiction of Beijing Municipality","award":["PHR20090510"],"award-info":[{"award-number":["PHR20090510"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["NSFC NO.81070799"],"award-info":[{"award-number":["NSFC NO.81070799"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Science Facility in Institutions of Higher Learning Under"},{"name":"jurisdiction of Beijing Municipality","award":["PXM 2009-014226-074691"],"award-info":[{"award-number":["PXM 2009-014226-074691"]}]},{"name":"Intramural Research program of the National Institute of Dental"},{"name":"Craniofacial Research, National Institutes of Health"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Periodontal ligament stem cells (PDLSCs) have provided novel cell sources for tooth and periodontal tissue regeneration. Allogeneic PDLSCs can reconstruct periodontal ligament tissue that has been damaged by periodontal diseases and regulate T-cell immunity. However, the effect of PDLSCs on B cells remains unknown. Here, we treated periodontitis in a miniature pig model using allogeneic PDLSCs and showed a reduction in humoral immunity in the animals. When cocultured with normal B cells, human PDLSCs (hPDLSCs) had similar effects as bone marrow mesenchymal stem cells in suppressing B cell proliferation, differentiation, and migration, while intriguingly, hPDLSCs increased B cell viability by secreting interleukin-6. Mechanistically, hPDLSCs suppressed B cell activation through cell-to-cell contact mostly mediated by programmed cell death protein 1 and programmed cell death 1 ligand 1. Our data revealed a previously unrecognized function of PDLSCs in regulating humoral immune responses, which may represent a novel therapeutic strategy for immune-related disorders.<\/jats:p>","DOI":"10.1002\/stem.1387","type":"journal-article","created":{"date-parts":[[2013,4,3]],"date-time":"2013-04-03T10:45:54Z","timestamp":1364985954000},"page":"1371-1382","source":"Crossref","is-referenced-by-count":86,"title":["Periodontal Ligament Stem Cells Regulate B Lymphocyte Function via Programmed Cell Death Protein 1"],"prefix":"10.1093","volume":"31","author":[{"given":"Ousheng","family":"Liu","sequence":"first","affiliation":[{"name":"Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, China"},{"name":"Department of Oral and Maxillofacial Surgery, Xiangya Hospital, Central South University, Changsha, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junji","family":"Xu","sequence":"additional","affiliation":[{"name":"Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Ding","sequence":"additional","affiliation":[{"name":"Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dayong","family":"Liu","sequence":"additional","affiliation":[{"name":"Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhipeng","family":"Fan","sequence":"additional","affiliation":[{"name":"Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunmei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanjun","family":"Chen","sequence":"additional","affiliation":[{"name":"National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaozhong","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Immunology, Capital Medical University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhangui","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Xiangya Hospital, Central South University, Changsha, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songlin","family":"Wang","sequence":"additional","affiliation":[{"name":"Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, China"},{"name":"Department of Biochemistry and Molecular Biology, Capital Medical University School of Basic Medical Sciences, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,7,5]]},"reference":[{"key":"2022011118252462600_bib1","first-page":"393","article-title":"The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells","volume":"3","author":"Friedenstein","year":"1970","journal-title":"Cell Tissue Kinet"},{"key":"2022011118252462600_bib2","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1038\/ncb1181","article-title":"A dermal niche for multipotent adult skin-derived precursor cells","volume":"6","author":"Fernandes","year":"2004","journal-title":"Nat Cell Biol"},{"key":"2022011118252462600_bib3","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1634\/stemcells.2004-0134","article-title":"Isolation and characterization of multipotent skin-derived precursors from human skin","volume":"23","author":"Toma","year":"2005","journal-title":"Stem Cells"},{"key":"2022011118252462600_bib4","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.brainres.2007.09.005","article-title":"Systemic transplantation of human adipose stem cells attenuated cerebral inflammation and degeneration in a hemorrhage stroke model","volume":"1183","author":"Kim","year":"2007","journal-title":"Brain Res"},{"key":"2022011118252462600_bib5","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1038\/nm1630","article-title":"Identification of tendon stem\/progenitor cells and the role of the extracellular matrix in their niche","volume":"13","author":"Bi","year":"2007","journal-title":"Nat Med"},{"key":"2022011118252462600_bib6","doi-asserted-by":"crossref","first-page":"3438","DOI":"10.1182\/blood-2006-11-055566","article-title":"Multipotent cells can be generated in vitro from several adult human organs (heart, liver, and bone marrow)","volume":"110","author":"Beltrami","year":"2007","journal-title":"Blood"},{"key":"2022011118252462600_bib7","doi-asserted-by":"crossref","first-page":"2466","DOI":"10.1634\/stemcells.2006-0071","article-title":"Placenta-derived multipotentcells exhibit immunosuppressive properties that are enhanced in the presence of interferon-\u03b3","volume":"24","author":"Chang","year":"2006","journal-title":"Stem Cells"},{"key":"2022011118252462600_bib8","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1182\/blood-2003-04-1291","article-title":"Amniotic fluid as a novel source of mesenchymal stem cells for therapeutic transplantation","volume":"102","author":"In't Anker","year":"2003","journal-title":"Blood"},{"key":"2022011118252462600_bib9","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.cellimm.2008.04.003","article-title":"Immunological properties of umbilical cord blood-derived mesenchymal stromal cells","volume":"251","author":"Oh","year":"2008","journal-title":"Cell Immunol"},{"key":"2022011118252462600_bib10","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1038\/nri2395","article-title":"Mesenchymal stem cells in health and disease","volume":"8","author":"Uccelli","year":"2008","journal-title":"Nat Rev Immunol"},{"key":"2022011118252462600_bib11","doi-asserted-by":"crossref","first-page":"3142","DOI":"10.1182\/blood-2011-11-391144","article-title":"Allogeneic mesenchymal stem cell treatment alleviates experimental and clinical Sjogren's syndrome","volume":"120","author":"Xu","year":"2012","journal-title":"Blood"},{"key":"2022011118252462600_bib12","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1002\/stem.68","article-title":"Mesenchymal stem cell transplantation reverses multiorgan dysfunction in systemic lupus erythematosus mice and humans","volume":"27","author":"Sun","year":"2009","journal-title":"Stem Cells"},{"key":"2022011118252462600_bib13","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1111\/j.1600-0757.2006.00169.x","article-title":"Clinical relevance of the host responses of periodontitis","volume":"43","author":"Kinane","year":"2007","journal-title":"Periodontol 2000"},{"key":"2022011118252462600_bib14","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1177\/154405910508401114","article-title":"CD14 and TLR4 gene polymorphisms in adult periodontitis","volume":"84","author":"Laine","year":"2005","journal-title":"J Dent Res"},{"key":"2022011118252462600_bib15","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1111\/jcpe.12009","article-title":"Mesenchymal stem cells derived from inflamed periodontal ligament loss the function of immunomodulation","volume":"39","author":"Liu","year":"2012","journal-title":"J Clin Periodontol"},{"key":"2022011118252462600_bib16","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/S0140-6736(04)16627-0","article-title":"Investigation of multipotent postnatal stem cells from human periodontal ligament","volume":"364","author":"Seo","year":"2004","journal-title":"Lancet"},{"key":"2022011118252462600_bib17","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1634\/stemcells.2007-0734","article-title":"Periodontal ligament stem cell-mediated treatment for periodontitis in miniature swine","volume":"26","author":"Liu","year":"2008","journal-title":"Stem Cells"},{"key":"2022011118252462600_bib18","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1002\/stem.512","article-title":"Allogeneic periodontal ligament stem cell therapy for periodontitis in swine","volume":"28","author":"Ding","year":"2010","journal-title":"Stem Cells"},{"key":"2022011118252462600_bib19","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1046\/j.1365-2249.1999.00819.x","article-title":"Humoral immune responses in periodontal disease may have mucosal and systemic immune features","volume":"115","author":"Kinane","year":"1999","journal-title":"Clin Exp Immunol"},{"key":"2022011118252462600_bib20","doi-asserted-by":"crossref","first-page":"1766","DOI":"10.1128\/CVI.00272-09","article-title":"Immunoglobulin G (IgG) class, but Not IgA or IgM, antibodies to peptides of the Porphyromonas gingivalis chaperone HtpG predict health in subjects with periodontitis by a fluorescence enzyme-linked immunosorbent assay","volume":"16","author":"Sweier","year":"2009","journal-title":"Clin Vaccine Immunol"},{"key":"2022011118252462600_bib21","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1038\/nbt0602-587","article-title":"Bone formation by human postnatal bone marrow stromal stem cells is enhanced by telomerase expression","volume":"20","author":"Shi","year":"2002","journal-title":"Nat Biotechnol"},{"key":"2022011118252462600_bib22","doi-asserted-by":"crossref","first-page":"e79","DOI":"10.1371\/journal.pone.0000079","article-title":"Mesenchymal stem cell-mediated functional tooth regeneration in swine","volume":"1","author":"Sonoyama","year":"2006","journal-title":"Plos One"},{"key":"2022011118252462600_bib23","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1158\/1078-0432.CCR-1182-3","article-title":"CCL19 and CXCL12 trigger in vitro chemotaxis of human mantle cell lymphoma B cells","volume":"10","author":"Corcione","year":"2004","journal-title":"Clin Cancer Res"},{"key":"2022011118252462600_bib24","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1093\/intimm\/dxf054","article-title":"Chemotaxis of human tonsil B lymphocytes to CC chemokine receptor (CCR) 1, CCR2 and CCR4 ligands is restricted to non-germinal center cells","volume":"14","author":"Corcione","year":"2002","journal-title":"Int Immunol"},{"key":"2022011118252462600_bib25","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1182\/blood-2005-07-2657","article-title":"Human mesenchymal stem cells modulate B-cell functions","volume":"107","author":"Corcione","year":"2006","journal-title":"Blood"},{"key":"2022011118252462600_bib26","doi-asserted-by":"crossref","first-page":"2098","DOI":"10.1126\/science.286.5447.2098","article-title":"Chemokines and cell migration in secondary lymphoid organs","volume":"286","author":"Cyster","year":"1999","journal-title":"Science"},{"key":"2022011118252462600_bib27","doi-asserted-by":"crossref","first-page":"596","DOI":"10.3858\/emm.2011.43.10.069","article-title":"In vitro migration capacity of human adipose tissue-derived mesenchymal stem cells reflects their expression of receptors for chemokines and growth factors","volume":"43","author":"Sun","year":"2011","journal-title":"Exp Mol Med"},{"key":"2022011118252462600_bib28","doi-asserted-by":"crossref","first-page":"9317","DOI":"10.1073\/pnas.97.16.9317","article-title":"Interleukin-6 is anessential, corticotropin-releasing hormone-independent stimulator of the adrenal axis during immune system activation","volume":"97","author":"Bethin","year":"2000","journal-title":"Proc Natl Acad Sci"},{"key":"2022011118252462600_bib29","first-page":"2281","article-title":"Human breast adipocytes express interleukin-6 (IL-6) and its receptor system: increased IL-6 production by beta-adrenergic activation and effects of IL-6 on adipocyte function","volume":"86","author":"Path","year":"2001","journal-title":"J Clin Endocrinol Metab"},{"key":"2022011118252462600_bib30","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1146\/annurev.med.51.1.245","article-title":"Age-associated increased interleukin-6 gene expression, late-life diseases, and frailty","volume":"51","author":"Ershler","year":"2000","journal-title":"Annu Rev Med"},{"key":"2022011118252462600_bib31","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1084\/jem.192.7.1027","article-title":"Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation","volume":"192","author":"Freeman","year":"2000","journal-title":"J Exp Med"},{"key":"2022011118252462600_bib32","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/85330","article-title":"PD-L2 is a second ligand for PD-1 and inhibits T cell activation","volume":"2","author":"Latchman","year":"2001","journal-title":"Nat Immunol"},{"key":"2022011118252462600_bib33","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1038\/ni.1877","article-title":"PD-1 regulates germinal center B cell survival and the formation and affinity of long-lived plasma cells","volume":"11","author":"Good-Jacobson","year":"2010","journal-title":"Nat Immunol"},{"key":"2022011118252462600_bib34","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1634\/stemcells.2007-0528","article-title":"Bone marrow-derived mesenchymal stem cells induce both polyclonal expansion and differentiation of B cells isolated from healthy donors and systemic lupus erythematosus patients","volume":"26","author":"Elisabetta","year":"2008","journal-title":"Stem Cells"},{"key":"2022011118252462600_bib35","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1182\/blood-2005-04-1496","article-title":"Mesenchymalstem cells ameliorate experimental auto immune encephalomyelitis inducing T cell anergy","volume":"106","author":"Zappia","year":"2005","journal-title":"Blood"},{"key":"2022011118252462600_bib36","doi-asserted-by":"crossref","first-page":"4120","DOI":"10.1182\/blood-2004-02-0586","article-title":"Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells","volume":"105","author":"Jiang","year":"2005","journal-title":"Blood"},{"key":"2022011118252462600_bib37","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.1182\/blood-2004-04-1559","article-title":"Human mesenchymal stem cells modulate allogeneic immune cell responses","volume":"105","author":"Aggarwal","year":"2005","journal-title":"Blood"},{"key":"2022011118252462600_bib38","doi-asserted-by":"crossref","first-page":"2214","DOI":"10.1182\/blood-2004-07-2921","article-title":"Human mesenchymal stem cells alter antigen-presenting cell maturation and induce T-cell unresponsiveness","volume":"105","author":"Beyth","year":"2005","journal-title":"Blood"},{"key":"2022011118252462600_bib39","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1006\/cimm.1994.1079","article-title":"Prostaglandin E2 inhibits B lymphocyte activation by a cAMP-dependent mechanism: PGE-inducible regulatory proteins","volume":"154","author":"Rachel","year":"1994","journal-title":"Cell Immunol"},{"key":"2022011118252462600_bib40","doi-asserted-by":"crossref","first-page":"4991","DOI":"10.1182\/blood-2008-07-166892","article-title":"Mesenchymal stromal cell-derived CCL2 suppresses plasma cell immunoglobulin production via STAT3 in activation and PAX5 induction","volume":"112","author":"Rafei","year":"2008","journal-title":"Blood"},{"key":"2022011118252462600_bib41","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.3324\/haematol.12857","article-title":"The effect of mesenchymal stem cells on the viability, proliferation and differentiation of B-lymphocytes","volume":"93","author":"Soraya","year":"2008","journal-title":"Haematologica"},{"key":"2022011118252462600_bib42","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1016\/j.exphem.2009.01.005","article-title":"Mesenchymal stem cells suppress B cell terminal differentiation","volume":"37","author":"Sadaki","year":"2009","journal-title":"Exp Hematol"},{"key":"2022011118252462600_bib43","doi-asserted-by":"crossref","first-page":"6141","DOI":"10.1182\/blood-2011-08-374728","article-title":"CD73-generated extracellular adenosine in chronic lymphocytic leukemia creates local conditions counteracting drug-induced cell death","volume":"118","author":"Serra","year":"2011","journal-title":"Blood"},{"key":"2022011118252462600_bib44","doi-asserted-by":"crossref","first-page":"2141","DOI":"10.1172\/JCI61788","article-title":"Defective B cell tolerance in adenosine deaminase deficiency is corrected by gene therapy","volume":"122","author":"Sauer","year":"2012","journal-title":"J Clin Invest"},{"key":"2022011118252462600_bib45","doi-asserted-by":"crossref","first-page":"e45272","DOI":"10.1371\/journal.pone.0045272","article-title":"Mesenchymal stem cells repress Th17 molecular program through the PD-1 pathway","volume":"7","author":"Luz-Crawford","year":"2012","journal-title":"Plos One"},{"key":"2022011118252462600_bib46","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1093\/intimm\/dxs098","article-title":"PD-1 is a novel regulator of human B-cell activation","volume":"25","author":"Thibult","year":"2013","journal-title":"Int Immunol"},{"key":"2022011118252462600_bib47","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1189\/jlb.0309203","article-title":"Hyperactivated B cells in human inflammatory bowel disease","volume":"86","author":"Noronha","year":"2009","journal-title":"J Leukocyte Biol"},{"key":"2022011118252462600_bib48","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1002\/stem.269","article-title":"Mesenchymal stromal cells: current understanding and clinical status","volume":"28","author":"Salem","year":"2010","journal-title":"Stem Cells"},{"key":"2022011118252462600_bib49","article-title":"In vitro analysis of mesenchymal stem cells derived from human teeth and bone marrow","author":"Tamaki","year":"2012","journal-title":"Odontology"}],"container-title":["Stem Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fstem.1387","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/stem.1387","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/stem.1387","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/stmcls\/article-pdf\/31\/7\/1371\/41980235\/stmcls_31_7_1371.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/stmcls\/article-pdf\/31\/7\/1371\/41980235\/stmcls_31_7_1371.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,19]],"date-time":"2022-01-19T02:49:18Z","timestamp":1642560558000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/stmcls\/article\/31\/7\/1371-1382\/6408112"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,7,1]]},"references-count":49,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2013,7,5]]},"published-print":{"date-parts":[[2013,7,1]]}},"URL":"https:\/\/doi.org\/10.1002\/stem.1387","relation":{},"ISSN":["1066-5099","1549-4918"],"issn-type":[{"value":"1066-5099","type":"print"},{"value":"1549-4918","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2013,7,1]]},"published":{"date-parts":[[2013,7,1]]}}}