{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T11:20:04Z","timestamp":1790162404852,"version":"4.1.0"},"reference-count":39,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2019,7,20]],"date-time":"2019-07-20T00:00:00Z","timestamp":1563580800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010767","name":"Innovative Medicines Initiative","doi-asserted-by":"publisher","award":["115142"],"award-info":[{"award-number":["115142"]}],"id":[{"id":"10.13039\/501100010767","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011272","name":"FP7 Health","doi-asserted-by":"publisher","award":["FP7-HEALTH-F2-2012-305549"],"award-info":[{"award-number":["FP7-HEALTH-F2-2012-305549"]}],"id":[{"id":"10.13039\/100011272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006315","name":"ReumaNederland","doi-asserted-by":"publisher","award":["11-1-308"],"award-info":[{"award-number":["11-1-308"]}],"id":[{"id":"10.13039\/501100006315","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["Veni project 916.12.109"],"award-info":[{"award-number":["Veni project 916.12.109"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Lymph nodes (LNs) are highly organized structures where specific immune responses are initiated by dendritic cells (DCs). We investigated the frequency and distribution of human myeloid (mDCs) and plasmacytoid (pDCs) in LNs and blood during the earliest phases of rheumatoid arthritis (RA). We included 22 RA-risk individuals positive for IgM rheumatoid factor and\/or anti-citrullinated protein antibodies, 16 biological-na\u00efve RA patients and 8 healthy controls (HCs). DC subsets (CD1c+ mDCs and CD304+ pDCs) in LN tissue and paired peripheral blood were analyzed using flow cytometry and confocal microscopy. In blood of RA patients a significant decreased frequency of pDCs was found, with a similar trend for mDCs. In contrast, mDC frequencies were higher in RA compared with HCs and RA-risk individuals, especially in LN. Frequency of mDCs seemed higher in LNs compared to paired blood samples in all donors, while pDCs were higher in LNs only in RA patients. As expected, both mDCs and pDCs localized mainly in T-cell areas of LN tissue. In conclusion, compared with RA-risk individuals, mDCs and pDCs were enriched in the LN tissue of early-RA patients, while their frequency in RA-risk individuals was comparable to HCs. This may suggest that other antigen-presenting cells are responsible for initial breaks of tolerance, while mDCs and pDCs are involved in sustaining inflammation.<\/jats:p>","DOI":"10.3390\/cells8070756","type":"journal-article","created":{"date-parts":[[2019,7,22]],"date-time":"2019-07-22T02:55:37Z","timestamp":1563764137000},"page":"756","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Myeloid Dendritic Cells Are Enriched in Lymph Node Tissue of Early Rheumatoid Arthritis Patients but not in At Risk Individuals"],"prefix":"10.3390","volume":"8","author":[{"given":"T.H.","family":"Ramwadhdoebe","sequence":"first","affiliation":[{"name":"Department of Rheumatology &amp; Clinical Immunology, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands"},{"name":"Department of Experimental Immunology, Amsterdam Infection &amp; Immunity Institute, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.I.","family":"Ramos","sequence":"additional","affiliation":[{"name":"Department of Experimental Immunology, Amsterdam Infection &amp; Immunity Institute, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.I.","family":"Maijer","sequence":"additional","affiliation":[{"name":"Department of Rheumatology &amp; Clinical Immunology, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.P.","family":"van Lienden","sequence":"additional","affiliation":[{"name":"Department of Radiology, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Maas","sequence":"additional","affiliation":[{"name":"Department of Radiology, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.M.","family":"Gerlag","sequence":"additional","affiliation":[{"name":"Department of Rheumatology &amp; Clinical Immunology, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.P.","family":"Tak","sequence":"additional","affiliation":[{"name":"Department of Rheumatology &amp; Clinical Immunology, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.C.","family":"Lebre","sequence":"additional","affiliation":[{"name":"Department of Experimental Immunology, Amsterdam Infection &amp; Immunity Institute, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3346-8921","authenticated-orcid":false,"given":"L.G.M.","family":"van Baarsen","sequence":"additional","affiliation":[{"name":"Department of Rheumatology &amp; Clinical Immunology, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands"},{"name":"Department of Experimental Immunology, Amsterdam Infection &amp; Immunity Institute, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,7,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/S0092-8674(01)00448-2","article-title":"Dendritic cells as vectors for therapy","volume":"106","author":"Banchereau","year":"2001","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/32588","article-title":"Dendritic cells and the control of immunity","volume":"392","author":"Banchereau","year":"1998","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jaut.2015.07.011","article-title":"Regulatory dendritic cells in autoimmunity: A comprehensive review","volume":"63","author":"Liu","year":"2015","journal-title":"J. Autoimmun."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1038\/nri3477","article-title":"The role of dendritic cells in autoimmunity","volume":"13","author":"Ganguly","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1002\/art.1780390202","article-title":"Presentation of self peptides by dendritic cells: Possible implications for the pathogenesis of rheumatoid arthritis","volume":"39","author":"Thomas","year":"1996","journal-title":"Arthritis Rheum."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1146\/annurev-immunol-020711-074950","article-title":"The dendritic cell lineage: Ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting","volume":"31","author":"Merad","year":"2013","journal-title":"Annu. Rev. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"R15","DOI":"10.1186\/ar1864","article-title":"Enumeration and phenotypical analysis of distinct dendritic cell subsets in psoriatic arthritis and rheumatoid arthritis","volume":"8","author":"Jongbloed","year":"2006","journal-title":"Arthritis Res. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"940","DOI":"10.2353\/ajpath.2008.070703","article-title":"Rheumatoid arthritis synovium contains two subsets of CD83-DC-LAMP- dendritic cells with distinct cytokine profiles","volume":"172","author":"Lebre","year":"2008","journal-title":"Am. J. Pathol."},{"key":"ref_9","first-page":"35","article-title":"Dendritic cell subsets: Their roles in rheumatoid arthritis","volume":"33","author":"Lebre","year":"2008","journal-title":"Acta Reumatol. Port."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"233","DOI":"10.3389\/fimmu.2012.00233","article-title":"Dendritic cells a double-edge sword in autoimmune responses","volume":"3","author":"Amodio","year":"2012","journal-title":"Front. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1084\/jem.194.6.769","article-title":"Dendritic cells induce peripheral T cell unresponsiveness under steady state conditions in vivo","volume":"194","author":"Hawiger","year":"2001","journal-title":"J. Exp. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/j.it.2017.07.007","article-title":"Dendritic Cells As Inducers of Peripheral Tolerance","volume":"38","author":"Iberg","year":"2017","journal-title":"Trends Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/S0167-5699(00)01610-8","article-title":"How can dendritic cells cause autoimmune disease?","volume":"21","author":"Drakesmith","year":"2000","journal-title":"Immunol. Today"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"6378","DOI":"10.4049\/jimmunol.0903951","article-title":"Identifying the cells breaching self-tolerance in autoimmunity","volume":"184","author":"Benson","year":"2010","journal-title":"J. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.humimm.2009.02.006","article-title":"Dendritic cells in rheumatoid arthritis: Which subset should be used as a tool to induce tolerance?","volume":"70","author":"Lebre","year":"2009","journal-title":"Hum. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"963","DOI":"10.4049\/jimmunol.182.2.963","article-title":"Plasmacytoid dendritic cells regulate breach of self-tolerance in autoimmune arthritis","volume":"182","author":"Jongbloed","year":"2009","journal-title":"J. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1111\/j.1365-2567.2008.02875.x","article-title":"Dendritic cells modulated by innate immunity improve collagen-induced arthritis and induce regulatory T cells in vivo","volume":"126","author":"Jaen","year":"2009","journal-title":"Immunology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"7071","DOI":"10.4049\/jimmunol.169.12.7071","article-title":"A novel dendritic cell-induced model of erosive inflammatory arthritis: Distinct roles for dendritic cells in T cell activation and induction of local inflammation","volume":"169","author":"Leung","year":"2002","journal-title":"J. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"R155","DOI":"10.1186\/ar4338","article-title":"Intra-articular CD1c-expressing myeloid dendritic cells from rheumatoid arthritis patients express a unique set of T cell-attracting chemokines and spontaneously induce Th1, Th17 and Th2 cell activity","volume":"15","author":"Moret","year":"2013","journal-title":"Arthritis Res. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1002\/art.25037","article-title":"Novel role of plasmacytoid dendritic cells in humans: Induction of interleukin-10-producing Treg cells by plasmacytoid dendritic cells in patients with rheumatoid arthritis responding to therapy","volume":"62","author":"Kavousanaki","year":"2010","journal-title":"Arthritis Rheum."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2815","DOI":"10.4049\/jimmunol.173.4.2815","article-title":"Characterization and recruitment of plasmacytoid dendritic cells in synovial fluid and tissue of patients with chronic inflammatory arthritis","volume":"173","author":"Lande","year":"2004","journal-title":"J. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1093\/rheumatology\/kex506","article-title":"Can an increase in autoantibody levels predict arthritis in arthralgia patients?","volume":"57","author":"Stuiver","year":"2018","journal-title":"Rheumatol. (Oxf.)"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1136\/annrheumdis-2011-200990","article-title":"EULAR recommendations for terminology and research in individuals at risk of rheumatoid arthritis: Report from the Study Group for Risk Factors for Rheumatoid Arthritis","volume":"71","author":"Gerlag","year":"2012","journal-title":"Ann. Rheum. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1136\/ard.2010.138461","article-title":"2010 rheumatoid arthritis classification criteria: An American College of Rheumatology\/European League Against Rheumatism collaborative initiative","volume":"69","author":"Aletaha","year":"2010","journal-title":"Ann. Rheum. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1136\/annrheumdis-2012-201540","article-title":"Hunting for the pathogenesis of rheumatoid arthritis: Core-needle biopsy of inguinal lymph nodes as a new research tool","volume":"71","author":"Zijlstra","year":"2012","journal-title":"Ann. Rheum Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2759","DOI":"10.1038\/s41467-019-10697-w","article-title":"Identification of HIV transmitting CD11c(+) human epidermal dendritic cells","volume":"10","author":"Bertram","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Canavan, M., Walsh, A.M., Bhargava, V., Wade, S.M., McGarry, T., Marzaioli, V., Moran, B., Biniecka, M., Convery, H., and Wade, S. (2018). Enriched Cd141+ DCs in the joint are transcriptionally distinct, activated, and contribute to joint pathogenesis. JCI Insight, 3.","DOI":"10.1172\/jci.insight.95228"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1182\/blood-2008-06-165266","article-title":"Distinctive localization of antigen-presenting cells in human lymph nodes","volume":"113","author":"Angel","year":"2009","journal-title":"Blood"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1038\/11360","article-title":"Plasmacytoid monocytes migrate to inflamed lymph nodes and produce large amounts of type I interferon","volume":"5","author":"Cella","year":"1999","journal-title":"Nat. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.immuni.2009.07.005","article-title":"Type I interferon signaling in dendritic cells stimulates the development of lymph-node-resident T follicular helper cells","volume":"31","author":"Cucak","year":"2009","journal-title":"Immunity"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/S1074-7613(03)00208-5","article-title":"Plasmacytoid dendritic cells induce plasma cell differentiation through type I interferon and interleukin 6","volume":"19","author":"Jego","year":"2003","journal-title":"Immunity"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3058","DOI":"10.1182\/blood-2003-08-2972","article-title":"Plasmacytoid dendritic cells, antigen, and CpG-C license human B cells for plasma cell differentiation and immunoglobulin production in the absence of T-cell help","volume":"103","author":"Poeck","year":"2004","journal-title":"Blood"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1146\/annurev.immunol.26.021607.090254","article-title":"Migration of dendritic cell subsets and their precursors","volume":"26","author":"Randolph","year":"2008","journal-title":"Annu. Rev. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1182\/blood-2013-04-495424","article-title":"Human CD1c+ dendritic cells secrete high levels of IL-12 and potently prime cytotoxic T-cell responses","volume":"122","author":"Nizzoli","year":"2013","journal-title":"Blood"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.immuni.2009.04.016","article-title":"Human dendritic cells induce the differentiation of interleukin-21-producing T follicular helper-like cells through interleukin-12","volume":"31","author":"Schmitt","year":"2009","journal-title":"Immunity"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.autrev.2012.07.011","article-title":"Potential roles for CD8(+) T cells in rheumatoid arthritis","volume":"12","author":"Carvalheiro","year":"2013","journal-title":"Autoimmun. Rev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/nrrheum.2016.74","article-title":"CD8(+) T cells in human autoimmune arthritis: The unusual suspects","volume":"12","author":"Petrelli","year":"2016","journal-title":"Nat. Rev. Rheumatol"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1111\/cei.13256","article-title":"Dendritic cells, T cells and their interaction in rheumatoid arthritis","volume":"196","author":"Wehr","year":"2019","journal-title":"Clin. Exp. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1038\/icb.2010.28","article-title":"Dendritic cells and humoral immunity in humans","volume":"88","author":"Ueno","year":"2010","journal-title":"Immunol. Cell Biol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/8\/7\/756\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:07:51Z","timestamp":1760188071000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/8\/7\/756"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,20]]},"references-count":39,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2019,7]]}},"alternative-id":["cells8070756"],"URL":"https:\/\/doi.org\/10.3390\/cells8070756","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,20]]}}}