Photoaging: UV radiation-induced cGAS-STING signaling promotes the aging process in skin by remodeling the immune network.

IF 4.4 4区 医学 Q1 GERIATRICS & GERONTOLOGY
Antero Salminen, Kai Kaarniranta, Anu Kauppinen
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引用次数: 0

Abstract

Excessive exposure of the skin to UV radiaton (UVR) accelerates the aging process and leads to a photoaging state which involves similar pathological alterations to those occurring in chronological aging. UVR exposure, containing both UVA and UVB radiation, triggers cellular senescence and a chronic inflammatory state in skin. UVR promotes oxidative stress and a leakage of double-stranded DNA (dsDNA) from nuclei and mitochondria into the cytoplasm of keratinocytes and fibroblasts. It is recognized that cytosolic dsDNA is a specific danger signal which stimulates cytoplasmic DNA sensors. The activation of the signaling through the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) is a major defence and survival mechanism combatting against tissue injuries. There is abundant evidence that UVR exposure of skin stimulates cGAS-STING signaling which promotes cellular senescence and remodels both the local and systemic immune network. cGAS-STING signaling activates the IRF3 and NF-κB signaling pathways which trigger both pro-inflammatory and immunosuppressive responses. Moreover, cGAS-STING signaling stimulates inflammatory responses by activating the NLRP3 inflammasomes. Senescent fibroblasts secrete not only cytokines but also chemokines and colony-stimulating factors which induce myeloid differentiation and recruitment of immune cells into inflamed skin. Photoaging is associated with an immunosuppressive state in skin which is attributed to an expansion of immunosuppressive cells, such as Tregs. UVR-induced cGAS-STING signaling also stimulates the expression of PD-L1, a ligand for inhibitory immune checkpoint receptor, which evokes an exhaustion of effector immune cells. There is clear evidence that cGAS-STING signaling can also accelerate chronological aging by remodeling the immune network.

光老化:紫外线辐射诱导的cGAS-STING信号通过重塑免疫网络促进皮肤老化过程。
皮肤过度暴露于紫外线辐射(UVR)会加速衰老过程,并导致光老化状态,这种状态涉及与时间衰老相似的病理改变。UVR暴露,包含UVA和UVB辐射,会引发皮肤细胞衰老和慢性炎症状态。UVR促进氧化应激和双链DNA (dsDNA)从细胞核和线粒体渗漏到角质形成细胞和成纤维细胞的细胞质中。胞质dsDNA是刺激胞质DNA传感器的一种特殊危险信号。通过环GMP-AMP合成酶(cGAS)-干扰素基因刺激因子(STING)激活信号是对抗组织损伤的主要防御和生存机制。大量证据表明,皮肤暴露在紫外线下会刺激cGAS-STING信号,从而促进细胞衰老,重塑局部和全身免疫网络。cGAS-STING信号通路激活IRF3和NF-κB信号通路,触发促炎和免疫抑制反应。此外,cGAS-STING信号通过激活NLRP3炎症小体刺激炎症反应。衰老的成纤维细胞不仅分泌细胞因子,还分泌趋化因子和集落刺激因子,诱导髓细胞分化和免疫细胞募集到炎症皮肤。光老化与皮肤的免疫抑制状态有关,这是由于免疫抑制细胞(如Tregs)的扩增。uvr诱导的cGAS-STING信号也刺激PD-L1的表达,PD-L1是抑制性免疫检查点受体的配体,引起效应免疫细胞的衰竭。有明确的证据表明,cGAS-STING信号也可以通过重塑免疫网络来加速时间顺序衰老。
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
Biogerontology
Biogerontology 医学-老年医学
CiteScore
8.00
自引率
4.40%
发文量
54
审稿时长
>12 weeks
期刊介绍: The journal Biogerontology offers a platform for research which aims primarily at achieving healthy old age accompanied by improved longevity. The focus is on efforts to understand, prevent, cure or minimize age-related impairments. Biogerontology provides a peer-reviewed forum for publishing original research data, new ideas and discussions on modulating the aging process by physical, chemical and biological means, including transgenic and knockout organisms; cell culture systems to develop new approaches and health care products for maintaining or recovering the lost biochemical functions; immunology, autoimmunity and infection in aging; vertebrates, invertebrates, micro-organisms and plants for experimental studies on genetic determinants of aging and longevity; biodemography and theoretical models linking aging and survival kinetics.
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