Department of Biochemistry and Molecular Biology, Signaling and Apoptosis and Genomics Research Group of the Hungarian Academy of Sciences, University of Debrecen, Debrecen, Hungary.
J Leukoc Biol. 2012 Jan;91(1):127-36. doi: 10.1189/jlb.0511243. Epub 2011 Oct 25.
GCs are powerful anti-inflammatory compounds inhibiting inflammatory cell recruitment and production of proinflammatory cytokines. We have recently found that DCs, the key players of T cell priming and polarization, respond to allogeneic apoptotic neutrophils with proinflammatory cytokine release and Th1 cell activation. Here, we show that monocyte-derived human DCs develop their capacity to engulf apoptotic cells by up-regulating a set of apoptophagocytic genes. This gene expression pattern was reprogrammed when differentiation took place in the presence of the synthetic GC Dex, which increased the expression of phagocytosis receptors MERTK and CD14, the bridging molecule C1QA, DNASE2, and ADORA3. The increased phagocytosis was attenuated by the addition of ADORA3 antagonist and could not be observed when bone marrow-derived DCs of ADORA3 KO mice were treated with Dex. The GC-treated human DCs loaded with allogeneic apoptotic neutrophils secreted, in response to LPS and IFN-γ, the inflammatory cytokine TNF-α. Furthermore, the Dex-treated DCs could activate autologous T lymphocytes toward Th1 effector cells, and this was enhanced by their exposure to allogeneic apoptotic neutrophils.
GC 是一种强大的抗炎化合物，可抑制炎症细胞的募集和促炎细胞因子的产生。我们最近发现，树突状细胞（DC）是 T 细胞启动和极化的关键细胞，它们会对同种异体凋亡中性粒细胞产生促炎细胞因子释放和 Th1 细胞激活反应。在这里，我们表明，单核细胞来源的人 DC 通过上调一组噬凋亡基因来发展吞噬凋亡细胞的能力。当在合成 GC Dex 的存在下发生分化时，这种基因表达模式被重新编程，这增加了吞噬受体 MERTK 和 CD14、桥接分子 C1QA、DNASE2 和 ADORA3 的表达。添加 ADORA3 拮抗剂可减弱吞噬作用，并且当用 Dex 处理 ADORA3 KO 小鼠的骨髓来源的 DC 时，无法观察到这种吞噬作用。用 Dex 处理的负载同种异体凋亡中性粒细胞的 GC 处理的人 DC 会分泌炎症细胞因子 TNF-α，以响应 LPS 和 IFN-γ。此外，用 Dex 处理的 DC 可以激活自身 T 淋巴细胞向 Th1 效应细胞，并且通过暴露于同种异体凋亡中性粒细胞而增强。
