Local immune cell contributions to fracture healing in aged individuals - A novel role for interleukin 22.
Local immune cell contributions to fracture healing in aged individuals - A novel role for interleukin 22.
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DOI：
10.1038/s12276-022-00834-9
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发表时间：
2022-08
影响因子：
12.8
通讯作者：
Schmidt-Bleek, Katharina
中科院分区：
文献类型：
--
作者：
Bucher, Christian H.;Berkmann, Julia C.;Burkhardt, Lisa-Marie;Paschke, Carolin;Schlundt, Claudia;Lang, Annemarie;Wolter, Angelique;Damerau, Alexandra;Geissler, Sven;Volk, Hans-Dieter;Duda, Georg N.;Schmidt-Bleek, Katharina
随着年龄的增长，骨折的风险增加，而再生能力下降。这种愈合潜力的变化似乎与适应性免疫有关，但其潜在机制仍不清楚。这项研究揭示了免疫老化/炎症，这会影响衰老个体的再生过程。在老化的临床前模型系统中，分析了不同水平的免疫老化，以确定将免疫老化/炎症条件与长骨骨折后骨形成联系起来的关键因素。在具有不同个体免疫老化水平的12月龄小鼠中，在损伤部位局部和全身监测与愈合结果相关的免疫学方面、祖细胞、微生物组和混杂因素。免疫老化组愈合过程中骨组织形成延迟，可能与细胞因子水平的显著变化相关。免疫细胞活化标志物上调、趋化因子受体可用性增加和抑制性信号传导缺乏导致促炎反应延长和放大。在免疫老化小鼠中，白细胞介素-22被鉴定为在延迟愈合中发挥核心作用的核心细胞信号蛋白。IL-22的治疗性中和逆转了这种特异性免疫老化相关的扰乱愈合。免疫老化被认为是老年人再生能力下降的一个影响因素。此外，中和IL-22的新治疗策略可以成功地使具有高级免疫经历的个体恢复愈合。中和一种关键的细胞因子，一种影响免疫系统的信号蛋白，可以在老年患者骨折后延长炎症反应后恢复愈合过程。骨折等损伤后，老年人的愈合模式差异很大，科学家们现在认为，患者的个体先天和适应性免疫特征直接影响愈合过程。短暂的促炎反应是启动健康愈合所必需的，但长期持续的反应可能是有害的。在对老年小鼠模型的实验中，由德国柏林朱利叶斯沃尔夫研究所的Katharina Schmidt-Bleek领导的研究小组证明，高水平的细胞因子白细胞介素-22会损害骨再生。白细胞介素-22水平升高是由于慢性炎症和炎症反应升高所致，在老年患者中普遍存在。研究小组对小鼠进行了治疗，以中和白细胞介素-22，从而加速愈合过程。
With increasing age, the risk of bone fractures increases while regenerative capacity decreases. This variation in healing potential appears to be linked to adaptive immunity, but the underlying mechanism is still unknown. This study sheds light on immunoaging/inflammaging, which impacts regenerative processes in aging individuals. In an aged preclinical model system, different levels of immunoaging were analyzed to identify key factors that connect immunoaged/inflammaged conditions with bone formation after long bone fracture. Immunological facets, progenitor cells, the microbiome, and confounders were monitored locally at the injury site and systemically in relation to healing outcomes in 12-month-old mice with distinct individual levels of immunoaging. Bone tissue formation during healing was delayed in the immunoaged group and could be associated with significant changes in cytokine levels. A prolonged and amplified pro-inflammatory reaction was caused by upregulated immune cell activation markers, increased chemokine receptor availability and a lack of inhibitory signaling. In immunoaged mice, interleukin-22 was identified as a core cell signaling protein that played a central role in delayed healing. Therapeutic neutralization of IL-22 reversed this specific immunoaging-related disturbed healing. Immunoaging was found to be an influencing factor of decreased regenerative capacity in aged individuals. Furthermore, a novel therapeutic strategy of neutralizing IL-22 may successfully rejuvenate healing in individuals with advanced immune experiences. Neutralizing a key cytokine, a signaling protein affecting the immune system could rejuvenate the healing process following prolonged inflammatory responses to bone fractures in elderly patients. Healing patterns vary widely in the elderly following injuries such as bone fractures, and scientists now believe that a patient’s individual innate and adaptive immune profile directly affects the healing process. A short-lived pro-inflammatory response is needed to kickstart healthy healing, but a longer-lasting response can be damaging. In experiments on aged mouse models, the team led by Katharina Schmidt-Bleek at the Julius Wolff Institute in Berlin, Germany, demonstrated that high levels of the cytokine interleukin-22 impaired bone regeneration. Elevated interleukin-22 levels resulted from chronically elevated inflammation and inflammaging, prevalent in elderly patients. The team treated the mice to neutralize interleukin-22, which accelerated the healing process.
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影响因子：
4
作者：
Baddoo, M;Hill, K;Phinney, DG
通讯作者：
Phinney, DG
影响因子：
4
作者：
Blume, S. W.;Curtis, J. R.
通讯作者：
Curtis, J. R.
影响因子：
5.5
作者：
El-Zayadi, Ahmed A.;Jones, Elena A.;McGonagle, Dennis
通讯作者：
McGonagle, Dennis
DOI：
10.1002/jor.23652
发表时间：
2018-01
期刊：
Journal of orthopaedic research : official publication of the Orthopaedic Research Society
影响因子：
--
作者：
Hebb JH;Ashley JW;McDaniel L;Lopas LA;Tobias J;Hankenson KD;Ahn J
通讯作者：
Ahn J
影响因子：
8.8
作者：
Boettcher, Jan P.;Schanz, Oliver;Knolle, Percy A.
通讯作者：
Knolle, Percy A.