Exosomes From Adipose-Derived Stem Cells Inhibit Skin T-Cell Activation and Alleviate Wound Inflammation

BACKGROUND: Skin T cells are essential for maintaining the skin's immune barrier and promoting early wound healing. Exosomes from adipose-derived stem cells (ADSCs-exo) can accelerate wound healing and reduce inflammation, but their impact on skin T-cell inflammation is unclear. OBJECTIVES: This study aims to explore ADSCs-exo's regulatory effects on skin T cells and wound inflammation. METHODS: ADSCs-exo were isolated by differential ultracentrifugation. An in vitro inflammation model using the human skin T-cell line HuT 78 was established to analyze the effects of ADSCs-exo on T-cell activation markers, inflammatory cytokines, and PI3K/Akt signaling. Apoptosis in HuT 78 cells was assessed with Calcein-AM/PI staining. A full-thickness skin injury model in C57 mice was used to evaluate ADSCs-exo's impact on dendritic epidermal T cells (DETCs) and inflammatory cytokine expression. RESULTS: Phorbol 12-myristate 13-acetate (PMA) enhanced interleukin (IL)-2, IL-17A, tumor necrosis factor alpha, and interferon gamma mRNA expression elevated T cell activation marker CD25 and reduced Akt/PI3K phosphorylation in HuT 78 cells, while inducing apoptosis. Although ADSCs-exo alone showed no CD25 modulation, their co-administration with PMA attenuated CD25 expression, inhibited IL-2 and IL-17A, and enhanced Akt/PI3K phosphorylation compared with PMA alone. Furthermore, ADSCs-exo can reverse the proapoptotic effect of PMA. In vivo, DETCs comprised 1% of mouse epidermal cells and increased at the wound margins postinjury. ADSCs-exo reduced both DETC recruitment and IL-17A levels during early wound healing. CONCLUSIONS: ADSCs-exo inhibited PMA-induced skin T-cell activation and inflammatory cytokine expression. Although acute trauma increased DETC expression at the wound site, ADSCs-exo inhibited early DETC and IL-17A expression, preventing excessive inflammation.