Department of Nephrology, Klinikum Rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany.
Amedes Holding AG, Ambulatory Healthcare Center (MVZ) Endokrinologikum München, Munich, Germany.
Front Immunol. 2024 May 10;15:1355824. doi: 10.3389/fimmu.2024.1355824. eCollection 2024.
levels are elevated in the blood and synovial fluid of patients with inflammatory arthritis. can be produced by Th17 cells and locally within joints by tissue-resident cells. induces osteoblast mineralization . As osteoproliferation and Th17 cells are important factors in the pathogenesis of axial spondyloarthritis (axSpA), we aimed to clarify the cellular sources of in spondyloarthritis.
Serum, peripheral blood mononuclear cells ( = 15-35) and synovial tissue ( = 3-9) of adult patients with axSpA, psoriatic arthritis (PsA) and rheumatoid arthritis (RA) and healthy controls (HCs, = 5) were evaluated by ELISA, flow cytometry including PrimeFlow assay, immunohistochemistry and immunofluorescence and quantitative PCR.
Synovial tissue of axSpA patients shows significantly more -positive cells than that of HCs ( < 0.01), but numbers are also elevated in PsA and RA patients. Immunofluorescence shows co-localization of with CD68, but not with CD3, SMA, CD163, cadherin-11, or CD90. is elevated in the serum of RA and PsA (but not axSpA) patients compared with HCs ( < 0.001 and < 0.01). However, peripheral blood CD4 T cells from axSpA and PsA patients show higher positivity for in the PrimeFlow assay compared with HCs. CD4 memory T cells from axSpA patients produce more under Th17-favoring conditions (IL-1β and IL-23) than cells from PsA and RA patients or HCs.
production is increased in the synovial tissue of SpA and can be localized to CD68 macrophage-like synoviocytes, whereas circulating Th17 cells are only modestly enriched. Considering the osteoproliferative properties of , this offers new therapeutic options independent of Th17 pathways.
在炎症性关节炎患者的血液和滑液中,水平升高。可以由 Th17 细胞产生,并在关节内由组织驻留细胞产生。诱导成骨细胞矿化。由于骨增生和 Th17 细胞是强直性脊柱炎(axSpA)发病机制中的重要因素,我们旨在阐明 spondyloarthritis 中 的细胞来源。
通过 ELISA、流式细胞术(包括 PrimeFlow 检测)、免疫组织化学和免疫荧光以及定量 PCR,评估了 axSpA、银屑病关节炎(PsA)和类风湿关节炎(RA)成年患者的血清、外周血单核细胞(= 15-35)和滑膜组织(= 3-9)以及健康对照者(HCs,= 5)的情况。
axSpA 患者的滑膜组织显示出明显比 HCs 更多的 -阳性细胞(<0.01),但 PsA 和 RA 患者的数量也升高。免疫荧光显示与 CD68 共定位,但与 CD3、SMA、CD163、钙黏蛋白-11 或 CD90 不共定位。与 HCs 相比,RA 和 PsA 患者的血清中水平升高(<0.001 和 <0.01)。然而,axSpA 和 PsA 患者的外周血 CD4 T 细胞在 PrimeFlow 检测中比 HCs 的阳性率更高。axSpA 患者的 CD4 记忆 T 细胞在 Th17 有利条件(IL-1β 和 IL-23)下产生更多的 ,而不是来自 PsA 和 RA 患者或 HCs 的细胞。
SpA 的滑膜组织中 产量增加,并且可以定位于 CD68 巨噬细胞样滑膜细胞,而循环中的 Th17 细胞只是适度富集。考虑到 的促骨增生特性,这提供了独立于 Th17 途径的新的治疗选择。