Mice with heterozygous deficiency of manganese superoxide dismutase (SOD2) have a skin immune system with features of “inflamm-aging”
Mice with heterozygous deficiency of manganese superoxide dismutase (SOD2) have a skin immune system with features of “inflamm-aging”
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DOI：
10.1007/s00403-013-1389-7
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发表时间：
2014-03
影响因子：
3
通讯作者：
J. Scheurmann;N. Treiber;C. Weber;A. Renkl;D. Frenzel;F. Trenz-Buback;A. Ruess;Guido Schulz;K. Scharffetter-Kochanek;J. Weiss
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文献类型：
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作者：
J. Scheurmann;N. Treiber;C. Weber;A. Renkl;D. Frenzel;F. Trenz-Buback;A. Ruess;Guido Schulz;K. Scharffetter-Kochanek;J. Weiss
树突状细胞 (DC) 是调节皮肤免疫的核心。免疫衰老与慢性炎症状态相关。人们对 DC 对“炎症衰老”的贡献知之甚少。在确定朗格汉斯细胞 (LC) 数量时，我们发现老化表皮中的 LC 减少了 60%。活性氧（ROS）与衰老有关。线粒体锰超氧化物歧化酶 (SOD2) 处于抗氧化防御的第一道防线。我们研究了 SOD2 杂合小鼠 (SOD2+/-) 的 DC 功能，发现 4 个月大时，LC 数量没有改变，但活化的 LC 损害了 MHC-II 和 CD44 的表达。未成熟的 SOD2+/- DC 产生增加的促炎性 IL-6 以及趋化因子 CXCL1 和 CXCL2。攻击后，SOD2+/- DC 积累了 ROS。当 LPS 激活 SOD2+/- DC 时，它们上调 MHC-II、CD86 和 CD44 的效率较低。令人惊讶的是，尽管 SOD2+/- DC 在刺激 wt T 细胞方面的效力较弱，但 SOD2+/- 小鼠的体内接触超敏反应 (CHS) 增强。然而，即使用 SOD2+/- DC 刺激，SOD2+/- T 细胞也显示出增殖增加，这可能解释了 CHS 的增加。我们的研究结果表明，SOD2 是调节“炎症衰老”的候选分子，通过改变 DC 和 T 细胞功能来传递免疫抑制和促炎症信号。
Dendritic cells (DC) are central in regulating skin immunity. Immunosenescence is associated with a chronic inflammatory state. Little is known about the contribution of DC to “inflamm-aging”. When determining langerhans cell (LC) numbers, we found a 60 % reduction of LC in aged epidermis. Reactive oxygen species(ROS) are linked with aging. The mitochondrial manganese superoxide dismutase (SOD2) is in the first line of antioxidant defense. We investigated the function of DC from SOD2 heterozygous mice (SOD2+/−) and found that at 4 months of age LC numbers are not altered, but activated LC have impaired expression of MHC-II and CD44. Immature SOD2+/− DC produced increased proinflammatory IL-6 and chemokines CXCL1 and CXCL2. Upon challenge SOD2+/− DC accumulated ROS. When activating SOD2+/− DC by LPS they less efficiently upregulated MHC-II, CD86 and CD44. Surprisingly, in vivo contact hypersensitivity (CHS) was enhanced in SOD2+/− mice although SOD2+/− DC were less potent in stimulating wt T cells. However, SOD2+/− T cells showed increased proliferation, even when stimulated with SOD2+/− DC, possibly explaining the increased CHS. Our findings suggest that SOD2 is a molecular candidate in the regulation of “inflamm-aging” conveying both immunosuppressive and proinflammatory signals through alteration of DC and T cell functions.