{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T04:12:53Z","timestamp":1792815173680,"version":"4.5.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T00:00:00Z","timestamp":1633564800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To examine the role of synovial CD1c<jats:sup>+<\/jats:sup>DCs in patients with Inflammatory Arthritis (IA) with a specific focus on the transcriptional and maturation signatures that govern their function.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>RNA sequencing was performed on healthy control (HC) peripheral blood (PB), IA PB, and IA synovial fluid (SF) CD1c<jats:sup>+<\/jats:sup>DCs. Multiparametric flow-cytometry and SPICE analysis were used to examine site [SF and Synovial Tissue (ST) CD1c+DCs] and disease specific characteristics of CD1c<jats:sup>+<\/jats:sup>DCs, while functional assays such as antigen processing, activation, and MMP production were also performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Increased frequency of CD1c<jats:sup>+<\/jats:sup>DCs (p&amp;lt;0.01) with a concomitant increase in CD80, CCR7 (p&amp;lt;0.01), and CXCR3 (p&amp;lt;0.05) expression was identified in IA PB compared to HC PB. Enrichment of CD1c<jats:sup>+<\/jats:sup>DCs was identified in IA synovial tissue (ST) (p&amp;lt;0.01) and IA SF (p&amp;lt;0.0001) compared to IA PB, while RNAseq revealed distinct transcriptional variation between PB and SF CD1c<jats:sup>+<\/jats:sup>DCs. Flow cytometry revealed increased expression of CD83, CD80, PD-L1, and BTLA (all p&amp;lt;0.05) in IA SF CD1c<jats:sup>+<\/jats:sup>DCs compared to PB, while SPICE identified synovial cells with unique co-expression patterns, expressing multiple DC maturation markers simultaneously. Functionally, synovial CD1c<jats:sup>+<\/jats:sup>DCs are hyper-responsive to TLR7\/8 ligation (p&amp;lt;0.05), have decreased antigen processing capacity (p=0.07), and display dysregulated production of MMPs. Finally, examination of both synovial CD1c<jats:sup>+<\/jats:sup>DCs and synovial CD141<jats:sup>+<\/jats:sup>DCs revealed distinct maturation and transcriptomic profiles.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Synovial CD1c<jats:sup>+<\/jats:sup>DCs accumulate in the inflamed IA synovium in a variety of distinct poly-maturational states, distinguishing them transcriptionally and functionally from CD1c<jats:sup>+<\/jats:sup>DCs in the periphery and synovial CD141<jats:sup>+<\/jats:sup>DCs.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2021.745226","type":"journal-article","created":{"date-parts":[[2021,10,10]],"date-time":"2021-10-10T01:20:01Z","timestamp":1633828801000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":29,"title":["Functionally Mature CD1c+ Dendritic Cells Preferentially Accumulate in the Inflammatory Arthritis 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