Laboratory of Bioinformatics and Computational Biology, Division of Experimental and Translational Research, Brazilian National Cancer Institute (INCA), Rio de Janeiro 20231-050, Brazil.
Genomic Sciences and Biotechnology Program, Catholic University of Brasilia, Brasilia 70790-160, Brazil.
Cells. 2021 May 26;10(6):1323. doi: 10.3390/cells10061323.
The skin is our largest organ and the outermost protective barrier. Its aging reflects both intrinsic and extrinsic processes resulting from the constant insults it is exposed to. Aging in the skin is accompanied by specific epigenetic modifications, accumulation of senescent cells, reduced cellular proliferation/tissue renewal, altered extracellular matrix, and a proinflammatory environment favoring undesirable conditions, including disease onset. Macrophages (Mφ) are the most abundant immune cell type in the skin and comprise a group of heterogeneous and plastic cells that are key for skin homeostasis and host defense. However, they have also been implicated in orchestrating chronic inflammation during aging. Since Mφ are related to innate and adaptive immunity, it is possible that age-modified skin Mφ promote adaptive immunity exacerbation and exhaustion, favoring the emergence of proinflammatory pathologies, such as skin cancer. In this review, we will highlight recent findings pertaining to the effects of aging hallmarks over Mφ, supporting the recognition of such cell types as a driving force in skin inflammaging and age-related diseases. We will also present recent research targeting Mφ as potential therapeutic interventions in inflammatory skin disorders and cancer.
皮肤是人体最大的器官，也是最外层的保护屏障。它的衰老反映了内在和外在过程，这些过程源于它不断受到的各种伤害。皮肤的衰老伴随着特定的表观遗传修饰、衰老细胞的积累、细胞增殖/组织更新减少、细胞外基质改变以及促炎环境，这些都不利于健康，包括疾病的发生。巨噬细胞（Mφ）是皮肤中最丰富的免疫细胞类型，它们是一群异质且具有可塑性的细胞，对于皮肤的稳态和宿主防御至关重要。然而，它们也被认为在衰老过程中协调慢性炎症。由于 Mφ 与先天和适应性免疫有关，因此可以推测，衰老修饰的皮肤 Mφ 促进了适应性免疫的加剧和衰竭，有利于促炎病理的出现，如皮肤癌。在这篇综述中，我们将重点介绍衰老特征对 Mφ 的影响的最新发现，这些发现支持将这些细胞类型视为皮肤炎症和与年龄相关疾病的驱动力。我们还将介绍针对 Mφ 的最新研究，这些研究将 Mφ 作为治疗炎症性皮肤疾病和癌症的潜在治疗靶点。
