Impaired Epidermal to Dendritic T Cell Signaling Slows Wound Repair in Aged Skin.
Impaired Epidermal to Dendritic T Cell Signaling Slows Wound Repair in Aged Skin.
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DOI：
10.1016/j.cell.2016.10.052
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发表时间：
2016-11-17
期刊：
影响因子：
64.5
通讯作者：
Fuchs E
中科院分区：
文献类型：
--
作者：
Keyes BE;Liu S;Asare A;Naik S;Levorse J;Polak L;Lu CP;Nikolova M;Pasolli HA;Fuchs E
老化的皮肤愈合伤口的能力很差，增加了感染的可能性。受伤后恢复体内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通讯都受到损害，从而降低了它们在受伤后恢复皮肤屏障的效率。在伤口边缘，老化的角质形成细胞的增殖和迁移减少。它们还表现出转录激活上皮免疫串扰调节因子的能力减弱，包括无法正确激活/维持树突上皮 T 细胞 (DETC)，而树突上皮 T 细胞在损伤后促进上皮再形成。通过探究机制，我们发现伤口边缘附近的老化角质形成细胞不能有效上调 Skints 或激活 STAT3。值得注意的是，当年轻皮肤中的表皮 Stat3、Skints 或 DETC 沉默时，受伤后的上皮再生就会受到干扰。这些发现强调了上皮免疫串扰扰动，特别是 Skints，是与年龄相关的伤口修复能力下降的关键介质。皮肤上皮细胞和免疫细胞之间的通讯逐渐丧失，导致与衰老相关的伤口愈合速度减慢。
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 up-regulate 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. Progressive loss of communication between epithelial and immune cells in the skin underlies the slow down in wound healing associated with aging.