Department of Immunology, Shandong University School of Medicine, 44# Wenhua Xi Road, Jinan 250012, China.
Mol Immunol. 2010 Jan;47(4):922-31. doi: 10.1016/j.molimm.2009.09.038. Epub 2009 Nov 12.
Dendritic cells (DCs) are often exposed to various oxygen tensions under physiological and pathological conditions. However, the effects of various oxygen tensions on DC functions remain unclear. In this study, we showed that hypoxia-differentiated DCs expressed lower levels of MHC-II molecule, co-stimulatory molecules (CD80, CD86) and proinflammatory cytokines (IL-1beta, IL-6, and TNF-alpha), but higher levels of immunoregulatory cytokine transforming growth factor-beta (TGF-beta) than normoxia-differentiated DCs. Unexpectedly, re-exposure of hypoxia-differentiated DCs to saturated oxygen (reoxygenation) completely restored their mature phenotype and function. Specifically, the reoxygenated DCs induced naïve CD4(+) T cells to differentiate into Th1 and Th17 effector cells, but deceased the generation of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs). The data indicate that hypoxic microenvironment suppresses the maturation and function of murine DCs. Reoxygenation of hypoxia-differentiated DCs however results in complete recovery of their mature phenotype and function, and has strong ability to drive immune response toward a proinflammatory direction, suggesting reoxygenated DCs may contribute to inflammation of ischemia-reperfusion injury.
树突状细胞（DCs）在生理和病理条件下经常暴露于各种氧张力下。然而，不同氧张力对 DC 功能的影响尚不清楚。在本研究中，我们表明，低氧分化的 DC 表达较低水平的 MHC-II 分子、共刺激分子（CD80、CD86）和前炎性细胞因子（IL-1β、IL-6 和 TNF-α），但高水平的免疫调节细胞因子转化生长因子-β（TGF-β）高于常氧分化的 DC。出乎意料的是，重新暴露于饱和氧（复氧）的低氧分化的 DC 完全恢复了它们的成熟表型和功能。具体而言，复氧的 DC 诱导幼稚 CD4+T 细胞分化为 Th1 和 Th17 效应细胞，但减少了 CD4+CD25+Foxp3+调节性 T 细胞（Tregs）的生成。数据表明，低氧微环境抑制了小鼠 DC 的成熟和功能。然而，低氧分化的 DC 的复氧导致其成熟表型和功能完全恢复，并且具有很强的能力将免疫反应推向促炎方向，这表明复氧的 DC 可能有助于缺血再灌注损伤的炎症。
