{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T03:29:52Z","timestamp":1792553392957,"version":"4.5.0"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,9]],"date-time":"2025-07-09T00:00:00Z","timestamp":1752019200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017628","name":"Ines Mandl Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017628","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010956","name":"State University of New York Upstate Medical University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010956","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Rheumatoid arthritis (RA) is a systemic autoimmune disease that leads to inflammation of synovial joints and other organs. Many RA patients \u201cshare\u201d a common peptide sequence within the HLA-DR (MHC II) molecule expressed on antigen-presenting cells (APC), suggesting that HLA-DR+ cells are important in RA inflammation. We use HLA-DR positivity to comprehensively immunophenotype APC by spectral cytometry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We measured mean fluorescence intensities (MFI) of HLA-DR and molecules associated with dendritic cells (CD141, CD1c, CD163, CD11c, CD123, and CD303), monocytes (CD14 and CD16), granulocytic markers (CD15 and CCR3), co-stimulatory molecules (CD86 and CD275), and chemokine receptors (CCR2, CCR3, and CCR7) from RA patients and healthy donors by spectral flow cytometry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      DC2 (CD1c+) showed higher CD86, CD275 (ICOS-L), CD56, and CCR7 in RA (all\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.05). CD56 was also increased in (CD163+) DC3 (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.0453). CD15 was increased throughout RA dendritic cell subsets and classical and intermediate monocytes (all\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.01). Except for B cells, HLA-DR was not different in RA. A distinct HLA-DR+CD15+CD16+ population appeared in RA (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.0004), which contributed a mean of 1.3% (\u00b1 SD 2.85%) to the overall HLA-DR+ APC compartment. This HLA-DR+CD15+CD16+ subset was positive for CD83, CD275, and, like plasmacytoid pDC, CD303+. However, in contrast to pDC, it formed distinct t-SNE clusters and differed from reference pDC (CD123+CD303+) by much less CD123 (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.01). The HLA-DR+CD15+CD16+ phenotype correlated with clinical markers of systemic inflammation (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.01).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>In conclusion, dendritic cell and monocyte alterations in RA include an increased co-stimulatory phenotype of CD1c+ DC2 and CD163+ DC3 with increased CD56 and CD15 in dendritic cells and monocytes. Moreover, the blood of RA patients contains HLA-DR+ cells with shared dendritic cell and granulocytic features. These phenotypic characterizations of RA patients implicate CD1c+ DC2 and CD163+ DC3 in the systemic autoimmune disease rheumatoid arthritis and suggest that increased HLA-DR+ phenotypes with shared granulocytic and dendritic cell features can contribute to RA, potentially by providing enhanced co-stimulatory presentation of self-antigen(s) to CD4+ T lymphocytes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1596609","type":"journal-article","created":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T05:47:02Z","timestamp":1752126422000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Spectral cytometry of rheumatoid arthritis patients implicates myeloid dendritic cells and granular HLA-DR+CD15+CD16+ cells in pro-inflammatory antigen presentation"],"prefix":"10.3389","volume":"16","author":[{"given":"Christian","family":"Geier","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haani","family":"Qudsi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estelle","family":"Khairallah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihad","family":"Ben Gabr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Winchester","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andras","family":"Perl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1004965","article-title":"The pathogenesis of rheumatoid arthritis","volume":"365","author":"McInnes","year":"2011","journal-title":"N Engl J Med"},{"key":"B2","doi-asserted-by":"publisher","first-page":"751-64","DOI":"10.1038\/s41577-022-00707-2","article-title":"A guide to antigen processing and presentation","volume":"22","author":"Pishesha","year":"2022","journal-title":"Nat Rev Immunol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780301102","article-title":"The shared epitope hypothesis. 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