Senescence-induced changes in CD4 T cell differentiation can be alleviated by treatment with senolytics.
Senescence-induced changes in CD4 T cell differentiation can be alleviated by treatment with senolytics.
复制标题
衰老引起的CD4 T细胞分化变化可以通过用鼻溶液治疗来缓解。
DOI：
10.1111/acel.13525
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发表时间：
2022-01
期刊：
影响因子：
7.8
通讯作者：
Haynes L
中科院分区：
文献类型：
--
作者：
Lorenzo EC;Torrance BL;Keilich SR;Al-Naggar I;Harrison A;Xu M;Bartley JM;Haynes L
衰老和衰老影响流感感染期间 CD4 T 辅助细胞 (Th) 亚群的分化。与年轻小鼠相比，在受感染的老年小鼠肺部，表达转录因子 FoxP3 的 Th 细胞比例显着更高，这表明存在调节性 CD4 T 细胞 (Treg)。驱动 FoxP3 表达的 TGF-β 水平在老年小鼠的支气管肺泡灌洗液中也较高，并且阻断 TGF-β 降低了流感感染期间老年肺部中 FoxP3+ Th 的百分比。由于 TGF-β 可能是衰老细胞的产物，因此可以通过衰老药物治疗来靶向这些细胞。在感染流感之前用 senolytics 治疗老年小鼠，可使这些老年小鼠的 Th 细胞分化恢复到更年轻的表型，其中表达 FoxP3 的 Th 细胞较少。此外，使用抗衰老药物治疗可诱导衰老的 Th 向愈合型 2 型表型分化，从而促进体内平衡的恢复。这些结果表明，衰老细胞通过产生 TGF-β 等细胞因子，对 Th 分化具有显着影响。在年轻小鼠中，CD4 T 细胞针对流感感染进行适当分化，产生参与抗病毒反应的 T 辅助子亚群。这种分化在老年小鼠中是异常的，但当老年小鼠接受 senolytics 治疗时可以得到改善。
Aging and senescence impact CD4 T helper cell (Th) subset differentiation during influenza infection. In the lungs of infected aged mice, there were significantly greater percentages of Th cells expressing the transcription factor FoxP3, indicative of regulatory CD4 T cells (Treg), when compared to young. TGF‐beta levels, which drive FoxP3 expression, were also higher in the bronchoalveolar lavage of aged mice and blocking TGF‐beta reduced the percentage of FoxP3+ Th in aged lungs during influenza infection. Since TGF‐beta can be the product of senescent cells, these were targeted by treatment with senolytic drugs. Treatment of aged mice with senolytics prior to influenza infection restored the differentiation of Th cells in those aged mice to a more youthful phenotype with fewer Th cells expressing FoxP3. In addition, treatment with senolytic drugs induced differentiation of aged Th toward a healing Type 2 phenotype, which promotes a return to homeostasis. These results suggest that senescent cells, via production of cytokines such as TGF‐beta, have a significant impact on Th differentiation. In young mice, CD4 T cells differentiate appropriately in response to influenza infection, generating T helper subsets that participate in the anti‐viral response. This differentiation is aberrant in aged mice, but can be improved when aged mice are treated with senolytics.
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影响因子：
64.5
作者：
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影响因子：
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作者：
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影响因子：
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作者：
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