Association of CD90 Expression by CD14⁺ Dendritic‐Shaped Cells in Rheumatoid Arthritis Synovial Tissue With Chronic Inflammation

Abstract

Objective. CD14 + dendritic-shaped cells show a dendritic morphology under the electron microscopy and engage in a pseudoemperipolesis phenomenon with lymphocytes. CD90 has been used as a marker of a major subset of fibroblast-like synoviocytes in rheumatoid arthritis (RA). In this study, we investigated the significance of CD90 expression in CD14 + dendritic-shaped cells and its correlation with RA chronic inflammation.Methods. Double immunofluorescence staining for CD14 and CD90 was performed in the collected tissues, including 12 active RA synovial tissues. The localization of CD14 + CD90 + cells, the percentages of CD14 + CD90 + cells and vascular areas, the degree of synovitis, and clinical data were investigated. Furthermore, CD14 + CD90 + cells analyzed by flow cytometry (CD14 high CD90 intermediate (int) cells) were sorted from RA synovial cells, and we examined their potential to differentiate into dendritic cells.Results. Double immunofluorescence staining showed that CD14 + CD90 + cells were abundant in RA synovial tissues. The percentages of CD14 + CD90 + cells and vascular areas correlated with some of the Krenn synovitis scores, but neither showed a strong correlation with RA disease activity parameters. Flow cytometry analysis indicated that CD14 high CD90 int cells were more abundant in both peripheral blood samples and synovial tissues in patients with active RA. CD14 high CD90 int cells were more likely to differentiate into dendritic cells in vitro.Conclusion. CD14 + dendritic-shaped cells expressed CD90 in the perivascular areas of RA synovial tissues. These findings suggest that CD14 + CD90 + dendritic-shaped cells migrate from the peripheral blood to the synovial tissue, the site of inflammation, and may contribute to the chronic inflammation of RA as dendritic progenitor cells.

CD14+ Dendritic‐Shaped Cells Functioning as Dendritic Cells in Rheumatoid Arthritis Synovial Tissues

“…In the region called the cartilage/pannus junction (CPJ), where RA synovial tissues invade the bone (Figure 1C and D ), many CD14 high CD90 int cells were also observed. Although we have reported in a previous article that these CD14 high CD90 int cells correlate with synovitis, 17 these results suggest that CD14+ cells may play an important role in the pathogenesis of RA, causing inflammation and bone destruction depending on the conditions within the synovial tissues.…”

“…In our previous study, CD14+ cells exhibited a dendritic shape with long extending projections protecting adjacent plasma cells and lymphocytes in electron microscopy studies and formed cell‐to‐cell contacts with adjacent lymphocytes 7 . These CD14+ dendritic‐shaped cells express CD90 in the perivascular areas in the sublining layer of RA synovial tissues, and this expression is weaker away from the blood vessels 17 . In contrast, HLA‐DR was strongly expressed away from blood vessels.…”

“…The CD90+ fibroblasts are positively correlated with systemic markers of inflammation and synovial tissues inflammation 16 . We have reported that CD14+ dendritic‐shaped cells express CD90 in RA synovial tissues, especially in the perivascular areas of the sublining layer 17 . We therefore named these CD14 high CD90 intermediate(int) cells.…”

“… 16 We have reported that CD14+ dendritic‐shaped cells express CD90 in RA synovial tissues, especially in the perivascular areas of the sublining layer. 17 We therefore named these CD14 high CD90 intermediate(int) cells. The number of these cells was positively correlated with the degree of synovitis.…”

Role and mechanism of CD90+ fibroblasts in inflammatory diseases and malignant tumors

“…In wound healing, the differentiation of fibroblasts into myofibroblasts is an important component, and the fibroblast subpopulation that can differentiate into myofibroblasts is mainly CD90 + fibroblasts (CD90 − fibroblasts differentiate mainly into adipose fibroblasts), and the ECM of patients with diabetes mellitus (DM) exhibits fibroblast senescence, and their failure to differentiate to produce myofibroblasts leads to impaired wound healing (Kunkemoeller et al 2017 ). In terms of the inflammatory response, CD90 + fibroblasts are highly amplified in rheumatoid arthritis (RA) and function to promote joint tissue inflammation (Mizoguchi et al 2018 ; Varzideh et al 2022 ; Kurose et al 2022 ).…”