Impaired Epidermal to Dendritic T Cell Signaling Slows Wound Repair in Aged Skin.

IF 45.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cell Pub Date : 2016-11-17 DOI:10.1016/j.cell.2016.10.052

Brice E Keyes, Siqi Liu, Amma Asare, Shruti Naik, John Levorse, Lisa Polak, Catherine P Lu, Maria Nikolova, Hilda Amalia Pasolli, Elaine Fuchs

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引用次数: 0

Abstract

Aged skin heals wounds poorly, increasing susceptibility to infections. Restoring homeostasis after wounding requires the coordinated actions of epidermal and immune cells. Here we find that both intrinsic defects and communication with immune cells are impaired in aged keratinocytes, diminishing their efficiency in restoring the skin barrier after wounding. At the wound-edge, aged keratinocytes display reduced proliferation and migration. They also exhibit a dampened ability to transcriptionally activate epithelial-immune crosstalk regulators, including a failure to properly activate/maintain dendritic epithelial T cells (DETCs), which promote re-epithelialization following injury. Probing mechanism, we find that aged keratinocytes near the wound edge don't efficiently upregulate Skints or activate STAT3. Notably, when epidermal Stat3, Skints, or DETCs are silenced in young skin, re-epithelialization following wounding is perturbed. These findings underscore epithelial-immune crosstalk perturbations in general, and Skints in particular, as critical mediators in the age-related decline in wound-repair.

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表皮与树突状 T 细胞之间的信号传递受损会减缓老化皮肤的伤口修复速度

老化的皮肤伤口愈合能力差，更容易受到感染。伤口愈合后恢复平衡需要表皮细胞和免疫细胞的协调作用。在这里，我们发现老化角质形成细胞的内在缺陷和与免疫细胞的交流都受到了损害，从而降低了它们在创伤后恢复皮肤屏障的效率。在伤口边缘，老化角质形成细胞的增殖和迁移能力下降。它们还表现出转录激活上皮-免疫串联调节因子的能力减弱，包括不能适当激活/维持树突状上皮 T 细胞（DETCs），而 DETCs 能促进损伤后的再上皮化。在探究机制时，我们发现伤口边缘附近的老化角质细胞不能有效上调 Skints 或激活 STAT3。值得注意的是，当年轻皮肤的表皮 Stat3、Skints 或 DETCs 被沉默时，伤口后的再上皮化会受到干扰。这些发现强调了上皮-免疫串联干扰，尤其是 Skints，是与年龄相关的伤口修复能力下降的关键介质。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell 生物-生化与分子生物学

CiteScore

110.00

自引率

0.80%

发文量

396

审稿时长

2 months

期刊介绍： Cells is an international, peer-reviewed, open access journal that focuses on cell biology, molecular biology, and biophysics. It is affiliated with several societies, including the Spanish Society for Biochemistry and Molecular Biology (SEBBM), Nordic Autophagy Society (NAS), Spanish Society of Hematology and Hemotherapy (SEHH), and Society for Regenerative Medicine (Russian Federation) (RPO). The journal publishes research findings of significant importance in various areas of experimental biology, such as cell biology, molecular biology, neuroscience, immunology, virology, microbiology, cancer, human genetics, systems biology, signaling, and disease mechanisms and therapeutics. The primary criterion for considering papers is whether the results contribute to significant conceptual advances or raise thought-provoking questions and hypotheses related to interesting and important biological inquiries. In addition to primary research articles presented in four formats, Cells also features review and opinion articles in its "leading edge" section, discussing recent research advancements and topics of interest to its wide readership.