Kurose Rie, Satoh Takashi, Kurose Akira, Ishibashi Yasuyuki, Uzuki Miwa, Wakai Yuji, Sasaki Tomoyuki, Ishida Kinji, Ogasawara Katsutoshi, Sawai Takashi
Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Iwate Medical University, Morioka, Japan.
ACR Open Rheumatol. 2024 Jul;6(7):412-420. doi: 10.1002/acr2.11670. Epub 2024 Apr 18.
We previously reported that CD14+ dendritic-shaped cells exhibit a dendritic morphology, engage in pseudo-emperipolesis with lymphocytes, and express CD90 in the perivascular areas of rheumatoid arthritis (RA) synovial tissues. However, it remains unclear whether these CD14CD90 cells function as dendritic cells. In this study, we investigated the dendritic cell-differentiation potential of CD14CD90 cells.
The localization and number of CD14CD90 cells in RA synovial tissues and peripheral blood were examined. The dendritic cell-differentiation potential of CD14CD90 cells was examined by measuring interleukin-6 and tumor necrosis factor-α levels in the supernatant and CD83 and human leukocyte antigen (HLA)-DR expression in the cells after induction of dendritic cell differentiation. Synovial cells were co-cultured with lymphocytes, and the activation of these cells was examined.
CD14CD90 cells were abundant in RA synovial tissues, including the sublining layer and the pannus areas. Patients with untreated and active RA had significantly higher percentages of CD14CD90 cells in the peripheral blood and synovial tissues. In RA synovial cells, inflammatory cytokine levels increased with dendritic cell-differentiation culture, but CD83 and HLA-DR expression were significantly increased in the CD14CD90 cell group. When co-cultured with lymphocytes, cell numbers and inflammatory cytokine levels significantly increased in both groups of synovial cells after dendritic cell induction.
CD14+ cells migrate and spread from the circulating blood to RA synovial tissues while expressing CD90, and CD14CD90 cells in contact with lymphocytes differentiate into HLA-DR+ dendritic cells, which contribute to chronic inflammation in RA.
我们之前报道过,CD14+树突状细胞呈现树突形态,与淋巴细胞发生假同血细胞作用,并在类风湿关节炎(RA)滑膜组织的血管周围区域表达CD90。然而,这些CD14CD90细胞是否发挥树突状细胞的功能仍不清楚。在本研究中,我们调查了CD14CD90细胞的树突状细胞分化潜能。
检测RA滑膜组织和外周血中CD14CD90细胞的定位和数量。通过测量树突状细胞分化诱导后上清液中的白细胞介素-6和肿瘤坏死因子-α水平以及细胞中的CD83和人类白细胞抗原(HLA)-DR表达,来检测CD14CD90细胞的树突状细胞分化潜能。将滑膜细胞与淋巴细胞共培养,并检测这些细胞的活化情况。
CD14CD90细胞在RA滑膜组织中丰富,包括衬里层和血管翳区域。未经治疗的活动性RA患者外周血和滑膜组织中CD14CD90细胞的百分比显著更高。在RA滑膜细胞中,炎症细胞因子水平随着树突状细胞分化培养而增加,但CD14CD90细胞组中CD83和HLA-DR表达显著增加。当与淋巴细胞共培养时,树突状细胞诱导后两组滑膜细胞的细胞数量和炎症细胞因子水平均显著增加。
CD14+细胞在表达CD90的同时从循环血液迁移并扩散到RA滑膜组织,与淋巴细胞接触的CD14CD90细胞分化为HLA-DR+树突状细胞,这有助于RA中的慢性炎症。