Solá, PalomaMereu, ElisabettaBonjoch, JúliaCasado-Peláez, MartaPrats, NeusAguilera, MònicaReina García, Óscar, 1976-Blanco, EnriqueEsteller, ManelDi Croce, LucianoHeyn, HolgerSolanas, GuiomarAznar Benitah, Salvador2023-07-182023-07-182023Solá P, Mereu E, Bonjoch J, Casado-Peláez M, Prats N, Aguilera M, Reina O, Blanco E, Esteller M, Di Croce L, Heyn H, Solanas G, Benitah SA. Targeting lymphoid-derived IL-17 signaling to delay skin aging. Nat Aging. 2023 Jun;3(6):688-704. DOI: 10.1038/s43587-023-00431-z2662-8465http://hdl.handle.net/10230/57599Skin aging is characterized by structural and functional changes that contribute to age-associated frailty. This probably depends on synergy between alterations in the local niche and stem cell-intrinsic changes, underscored by proinflammatory microenvironments that drive pleotropic changes. The nature of these age-associated inflammatory cues, or how they affect tissue aging, is unknown. Based on single-cell RNA sequencing of the dermal compartment of mouse skin, we show a skew towards an IL-17-expressing phenotype of T helper cells, γδ T cells and innate lymphoid cells in aged skin. Importantly, in vivo blockade of IL-17 signaling during aging reduces the proinflammatory state of the skin, delaying the appearance of age-related traits. Mechanistically, aberrant IL-17 signals through NF-κB in epidermal cells to impair homeostatic functions while promoting an inflammatory state. Our results indicate that aged skin shows signs of chronic inflammation and that increased IL-17 signaling could be targeted to prevent age-associated skin ailments.application/pdfeng© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s43587-023-00431-zAgeingStem cellsinfo:eu-repo/semantics/openAccess