Skin‐Derived Precursors‐Derived Exosomes Alleviated Acne Inflammation via <scp>TLR2</scp> / <scp>MyD88</scp> / <scp>NF</scp> ‐ <scp>κB</scp> Signaling Pathway: In Vitro and In Vivo Studies

Skin-derived precursors (SKPs) isolated from the dermis are poorly immunogenic and capable of modulating the allogeneic immune responses. Previous studies implied mouse SKPs-derived exosomes (mSKPs-exo) might possess immunomodulatory functions. In the present study we collected mSKPs-exo using ultracentrifugation method and characterized them. We then explored mSKPs-exo's impact on acne inflammation with Cutibacterium acnes (C. acnes)-challenged murine monocyte-macrophages RAW264.7 and Sprague Dawley (SD) rats auricular acne model. The in vitro studies demonstrated mSKPs-exo reduced nitric oxide, TNF-α, and IL-6 concentration in C. acnes-challenged RAW264.7 cells supernatant. mSKPs-exo also ameliorated NF-κB p65 nuclear translocation and CD86 and iNOS antigens expression in C. acnes-challenged RAW264.7 cells. The RT-PCR and Western blots revealed mSKPs-exo alleviated inflammation by regulating key genes (TLR2, TNF-α, MyD88, and IL-6) and proteins (TLR2, MyD88, IκBa, and NF-κBp65) in the TLR2/MyD88/NF-κB pathway. The anti-inflammatory effects could be synergistically enhanced by IκB/IKK inhibitor. The in vivo studies validated mSKPs-exo's efficacy on acne inflammation and TLR2/MyD88/NF-κB pathway. Topical dermal injection of mSKPs-exo alleviated auricular inflammatory manifestations in SD rats. Immunohistochemistry and Western blot results indicated mSKPs-exo reduced the expression of TLR2, MyD88, MMP3, p-p38 MAPK, and NF-κB p65. The effect was comparable with topical adapalene gel application. The current study initiated mSKPs-exo research and provided theoretical support and experimental data for their potential application in inflammation regulation, acne treatment, and novel therapeutic targets identification.