| Autor: |
Solá Castrillo, Paloma, Mereu, Elisabetta, Bonjoch, Júlia, Casado Peláez, Marta, Prats, Neus, Aguilera, Mònica, Reina, Oscar, Blanco, Enrique, Esteller, Manel, Croce, Luciano Di, Heyn, Holger, Solanas Fuster, Guiomar, Benitah, Salvador A. |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Popis: |
Skin 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. Research in the S.A.B. laboratory is supported partially by the European Research Council under the European Union’s Horizon 2020 research and innovation program (grant agreement no. 787041), the Government of Cataluña (SGR grant), the Government of Spain (MINECO) and Foundation Lilliane Bettencourt. This work was partially supported by a Leonardo grant (BBVA Foundation) awarded to G.S. P.S. was awarded a Spanish Ministry of Economy and Development fellowship (MINECO, no. BES-2017-081279). J.B. was awarded a Spanish Ministry of Science and Innovation fellowship (MCI, no. PRE-2021-097118). M.E. and E.M. were supported by Ministerio de Ciencia e Innovación (MCI), Agencia Estatal de Investigación (AEI) and the European Development Regional Fund, ‘A way to make Europe’ ERDF (no. RTI2018-094049-B-I00). H.H. has received funding from Ministerio de Ciencia, Innovación y Universidades (no. SAF2017-89109-P; AEI/FEDER, UE). IRB Barcelona is a Severo Ochoa Center of Excellence (MINECO award no. SEV-2015-0505). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. We thank the histopathology, advanced digital microscopy and genomics facilities of IRB Barcelona and the genomics unit at CRG. We thank C. Niessen and E. Wachsmuth for useful tips on TEWL usage. We thank V. Raker for manuscript editing. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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