Exosomes are nano-sized vesicles (30–200 nm) constantly released by almost all cells. The ability of exosomes to travel between cells and deliver their cargo, which includes lipids, proteins, and nucleic acids, makes them an appealing cell-free therapy option to treat multiple diseases. Here, we investigated for the first time whether human adipose tissue-derived mesenchymal stem cell-derived exosomes can ameliorate atopic dermatitis (AD) in an in vivo mouse model. When injected either intravenously (IV) or subcutaneously (SC) into NC/Nga mice treated with house dust mite antigens, ERC-exosomes were found to reduce pathological symptoms such as clinical score, the levels of serum IgE, the number of eosinophils in blood, and the infiltration of mast cells, CD86+, and CD206+ cells in skin lesions. ERC-exosomes also significantly reduced mRNA expression of various inflammatory cytokines such as interleukin (IL)-4, IL-23, IL-31, and tumor necrosis factor (TNF-) in AD skin lesions of Nc/Nga mice. Taken together, these results suggest that ERC-exosomes can be a novel promising cell-free therapeutic modality for AD treatment. (Byong Seung Cho, Jin Ock Kim, Dae Hyun Ha and Yong Weon – Stem Cell Research Therapy, BioMedCentral.com)