Exosomes Derived from Adipose Stem Cells Inhibit Skin T Cells Activation and Alleviate Wound Inflammation.

Abstract

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) enhances IL-2, IL-17A, TNF-α, and IFN-γ mRNA expression, upregulates CD25 and CD69, and decreases Akt and PI3K phosphorylation in HuT 78 cells. PMA also promotes apoptosis. ADSCs-exo alone do not significantly affect CD25 and CD69 expression, but co-treatment with PMA and ADSCs-exo reduces CD25 and CD69 expression, inhibits IL-2 and IL-17A, and increases Akt and PI3K phosphorylation compared to PMA alone. Furthermore, ADSCs-exo can reverse the pro-apoptotic effect of PMA. In vivo, DETCs comprised 1% of mouse epidermal cells and increased at the wound margin post-injury. ADSCs-exo reduced DETC and IL-17A expression early in wound healing.

Conclusions: ADSCs-exo inhibited PMA-induced skin T cell activation and inflammatory cytokine expression. While acute trauma increased DETC expression at the wound site, ADSCs-exo inhibited early DETC and IL-17A expression, preventing excessive inflammation.