期刊
ARTHRITIS RESEARCH & THERAPY
卷 15, 期 6, 页码 -出版社
BMC
DOI: 10.1186/ar4403
关键词
-
类别
资金
- Fundacao para a Ciencia e a Tecnologia Portugal [SFRH/BD/47257/2008]
- Dutch Arthritis Association (Reumafonds), the Netherlands [7-1-301]
- Fundação para a Ciência e a Tecnologia [SFRH/BD/47257/2008] Funding Source: FCT
Introduction: The FMS-related tyrosine kinase 3 ligand (Flt3L)/CD135 axis plays a fundamental role in proliferation and differentiation of dendritic cells (DCs). As DCs play an important role in rheumatoid arthritis (RA) immunopathology we studied in detail the Flt3L/CD135 axis in RA patients. Methods: The levels of Flt3L in (paired) serum and synovial fluid (SF) were quantified by enzyme-link immunosorbent assay (ELISA). Expression of Flt3L and CD135 in paired peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) was quantified by fluorescence-activated cell sorting (FACS). The expression of Flt3L, CD135 and TNF-Converting Enzyme (TACE) in synovial tissues (STs) and in vitro polarized macrophages and monocyte-derived DCs (Mo-DCs) was assessed by quantitative PCR (qPCR). CD135 ST expression was evaluated by immunohistochemistry and TACE ST expression was assessed by immunofluorescence. Flt3L serum levels were assessed in RA patients treated with oral prednisolone or adalimumab. Results: Flt3L levels in RA serum, SF and ST were significantly elevated compared to gout patients and healthy individuals (HI). RA SF monocytes, natural killer cells and DCs expressed high levels of Flt3L and CD135 compared to HI. RA ST CD68(+) and CD163(+) macrophages, CD55(+) fibroblast-like synoviocytes (FLS), CD31(+) endothelial cells or infiltrating monocytes and CD19(+) B cells co-expressed TACE. IFN-gamma-differentiated macrophages expressed higher levels of Flt3L compared to other polarized macrophages. Importantly, Flt3L serum levels were reduced by effective therapy. Conclusions: The Flt3L/CD135 axis is active in RA patients and is responsive to both prednisolone and adalimumab treatment. Conceivably, this ligand receptor pair represents a novel therapeutic target.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据