Targeting lymphoid-derived IL-17 signaling to delay skin aging

Area of Science:

• Immunology
• Dermatology
• Aging Research

Background:

• Skin aging involves structural and functional decline, linked to local niche alterations and stem cell changes.
• Pro-inflammatory microenvironments significantly influence age-associated frailty and tissue aging.
• The specific inflammatory cues and their impact on skin aging remain largely unknown.

Purpose of the Study:

• To investigate the nature of age-associated inflammatory cues in mouse skin.
• To determine the role of IL-17 (interleukin-17) signaling in skin aging.
• To explore IL-17 blockade as a potential strategy to mitigate skin aging.

Main Methods:

• Single-cell RNA sequencing of the dermal compartment in aged mouse skin.
• In vivo blockade of IL-17 signaling during the aging process.
• Analysis of NF-κB signaling pathways in epidermal cells.

Main Results:

• Aged mouse skin shows a higher prevalence of IL-17-expressing T helper cells, γδ T cells, and innate lymphoid cells.
• In vivo IL-17 blockade reduced skin inflammation and delayed the onset of age-related skin traits.
• Aberrant IL-17 signaling activates NF-κB in epidermal cells, impairing homeostasis and promoting inflammation.

Conclusions:

• Aged skin is characterized by chronic inflammation, with IL-17 playing a key role.
• Targeting IL-17 signaling presents a promising therapeutic avenue for preventing age-associated skin ailments.
• Understanding IL-17's mechanism in epidermal cells offers insights into skin aging processes.