北京大学邱义福课题组发现，巨噬细胞中的2型细胞因子信号传导可防止细胞衰老和机体老化。该研究于2023年1月22日在线发表于国际一流学术期刊《免疫》。

研究人员报告了2型细胞因子信号缺乏会加速衰老，相反，白细胞介素-4（IL-4）-STAT6通路会保护巨噬细胞免于衰老。从机理上讲，活化的STAT6可通过同源重组和范可尼贫血症途径促进DNA修复相关基因的表达。相反，STAT6缺乏会诱导核DNA释放到细胞质中，从而促进组织炎症和机体衰老。

重要的是，研究人员证明了IL-4治疗能防止巨噬细胞衰老，并能改善老龄小鼠的健康寿命，其程度可与衰老治疗相媲美。总之，这些研究结果支持2型细胞因子信号传导能保护巨噬细胞免受免疫衰老的影响，因此具有改善健康衰老的治疗潜力。

据了解，器官和组织中衰老细胞的积累是衰老的标志，已知会导致与年龄相关的疾病。虽然与衰老相关的免疫功能失调或免疫衰老已知会导致这一过程，但其潜在机制仍然难以捉摸。

附：英文原文

Title: Type 2 cytokine signaling in macrophages protects from cellular senescence and organismal aging

Author: Zhao Zhou, Jingfei Yao, Dongmei Wu, Xun Huang, Yushuang Wang, Xinmeng Li, Qiang Lu, Yifu Qiu

Issue&Volume: 2023-01-22

Abstract: Accumulation of senescent cells in organs and tissues is a hallmark of aging and knownto contribute to age-related diseases. Although aging-associated immune dysfunction,or immunosenescence, is known to contribute to this process, the underlying mechanismremains elusive. Here, we report that type 2 cytokine signaling deficiency acceleratedaging and, conversely, that the interleukin-4 (IL-4)-STAT6 pathway protected macrophagesfrom senescence. Mechanistically, activated STAT6 promoted the expression of genesinvolved in DNA repair both via homologous recombination and Fanconi anemia pathways.Conversely, STAT6 deficiency induced release of nuclear DNA into the cytoplasm topromote tissue inflammation and organismal aging. Importantly, we demonstrate thatIL-4 treatment prevented macrophage senescence and improved the health span of agedmice to an extent comparable to senolytic treatment, with further additive effectswhen combined. Together, our findings support that type 2 cytokine signaling protectsmacrophages from immunosenescence and thus hold therapeutic potential for improvinghealthy aging.

DOI: 10.1016/j.immuni.2024.01.001

Source: https://www.cell.com/immunity/fulltext/S1074-7613(24)00026-8