Researchers show blocking IL-17’s function reduces the pro-inflammatory state and delays the appearance of age-related features in the skin.
A team of scientists from the Institute for Research in Biomedicine (IRB Barcelona) and the National Center for Genomic Analysis (CNAG) has made an interesting breakthrough in understanding the mechanisms underlying skin aging. Led by Dr Guiomar Solanas, Dr Salvador Aznar Benitah and Dr Holger Heyn, the researchers have discovered the central role played by the IL-17 protein in the aging process of the skin, shedding light an IL-17-mediated aging pathway, and highlighting its association with an inflammatory state .
Longevity.Technology: Aging skin undergoes a series of progressive structural and functional changes that contribute to its deterioration and fragility. As it ages, the skin’s capacity for regeneration decreases, its wound healing ability diminishes and the skin’s barrier function weakens. Understanding the cellular and molecular processes driving these changes is key to developing effective strategies to mitigate the adverse effects of aging on the skin.
The findings of this study, published in the journal Nature Aging, provide insights into the structural and functional changes that occur in aged skin and identify how some immune cells in the skin express high levels of IL-17 – knowledge that could open up new possibilities for therapeutic interventions.
“Our results show that IL-17 is involved in various functions related to ageing,” explains Dr Aznar Benitah, ICREA researcher and head of the Stem Cells and Cancer laboratory at IRB Barcelona. “We have observed that blocking the function of this protein slows down the appearance of various deficiencies associated with ageing skin. This discovery opens up new possibilities for treating some of the symptoms or facilitating skin recovery after surgery, for example .”
“Single cell sequencing has allowed us to dive deep into the complexity of cell types and states forming the skin and how these change during lifespan,” says Dr Holger Heyn, head of the Single Cell Genomics laboratory at CNAG. “We did not only find differences in the composition of aged skin, but also changes in cell activity states. Particularly immune cells showed specific age-related profiles, which we could pinpoint by analyzing thousands of individual cells one at a time .”
The skin not only consists of various types of epithelial cells and hair follicle cells but also houses immune cells that serve a vital role in preventing infections and safeguarding against damage. The study describes how, during aging, the presence of some of these immune cells, namely gamma delta T cells, innate lymphoid cells, and CD4+ T cells, significantly increases in the skin – these same cells also start expressing very high levels of the pro-inflammatory cytokine IL-17.
Dr Paloma Solá, the first author of the paper, along with Dr. Elisabetta Mereu, is now a researcher at the Josep Carreras Leukemia Research Institute. She explains: “Ageing is associated with a mild but persistent inflammatory state, and in the skin, this is characterised by a substantial increase in IL-17, which contributes to skin deterioration .”
Previous studies have linked IL-17 to autoimmune skin conditions like psoriasis, and treatments block this protein already exist. In this study, the researchers investigated the effects of blocking IL-17 activity on several aspects related to aging skin, including hair follicle growth, transepidermal water loss, wound healing and genetic markers of aging. Blocking IL-17 resulted in improvements in all four parameters, significantly delaying the acquisition of aging traits .
Dr Guiomar Solanas, an associate researcher at IRB Barcelona, emphasizes: “IL-17 protein is essential for vital body functions, such as defense against microbes and wound healing, so permanently blocking it would not be an option. What we have observed is that its temporary inhibition offers benefits that could be of interest at a therapeutic level .”
The researchers’ future investigations will focus on teasing out the aging processes associated with inflammatory states in the skin and how they are linked to IL-17. Furthermore, they aim to explore whether IL-17 is involved in the aging and deterioration of other tissues and organs. These endeavors will provide deeper insights into the intricate interplay between IL-17, inflammation and the ageing process, potentially uncovering new avenues for therapeutic interventions.