Macrophages Are Polarized toward an Inflammatory Phenotype by their Aged Microenvironment in the Human Skin

Abstract

Aging of the skin is accompanied by cellular as well as tissue environmental changes, ultimately reducing the ability of the tissue to regenerate and adequately respond to external stressors. Macrophages are important gatekeepers of tissue homeostasis, and it has been reported that their number and phenotype change during aging in a site-specific manner. How aging affects human skin macrophages and what implications this has for the aging process in the tissue are still not fully understood. Using single-cell RNA-sequencing analysis, we show that there is at least a 50% increase of macrophages in human aged skin, which appear to have developed from monocytes and exhibit more proinflammatory M1-like characteristics. In contrast, the cell-intrinsic ability of aged monocytes to differentiate into M1 macrophages was reduced. Using coculture experiments with aged dermal fibroblasts, we show that it is the aged microenvironment that drives a more proinflammatory phenotype of macrophages in the skin. This proinflammatory M1-like phenotype in turn negatively influenced the expression of extracellular matrix proteins by fibroblasts, emphasizing the impact of the aged macrophages on the skin phenotype. mehr

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Titel	Macrophages Are Polarized toward an Inflammatory Phenotype by their Aged Microenvironment in the Human Skin
Medien	The Journal of Investigative Dermatology
Heft	12
Band	142
ISSN	1523-1747
Verfasser	Leonie Gather, Neetika Nath, Cassandra Falckenhayn, Sergio Oterino-Sogo, Thomas Bosch, Horst Wenck, Marc Winnefeld, Elke Grönniger, Prof. Dr. Stefan Simm, Annette Siracusa
Seiten	3136–3145.e11
Veröffentlichungsdatum	12.2022
Zitation	Gather, Leonie; Nath, Neetika; Falckenhayn, Cassandra; Oterino-Sogo, Sergio; Bosch, Thomas; Wenck, Horst; Winnefeld, Marc; Grönniger, Elke; Simm, Stefan; Siracusa, Annette (2022): Macrophages Are Polarized toward an Inflammatory Phenotype by their Aged Microenvironment in the Human Skin. The Journal of Investigative Dermatology 142 (12), 3136–3145.e11. DOI: 10.1016/j.jid.2022.06.023