AUTHOR=Liu Jiaxi , Xu Zuyu , Yu Jinyan , Zang Xiao , Jiang Shangde , Xu Shuyue , Wang Wei , Hong Shanchao 

TITLE=MiR-146a-5p engineered hucMSC-derived extracellular vesicles attenuate Dermatophagoides farinae-induced allergic airway epithelial cell inflammation

JOURNAL=Frontiers in Immunology

VOLUME=Volume 15 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1443166

DOI=10.3389/fimmu.2024.1443166

ISSN=1664-3224

ABSTRACT=Allergic asthma is prevalent in children, with Dermatophagoides farinae (D. farinae) being a common indoor allergen. Current treatments for allergic airway inflammation are limited and carry risks. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) show promise as a cell-free therapeutic approach. However, the use of engineered extracellular vesicles (EVs) for D. farinae-induced allergic airway epithelial cell inflammation remains unexplored. This study generated miR-146a-5p-engineered EVs (146a-EVs) from human umbilical cord mesenchymal stem cells (hucMSCs) and established D. farinae induced mouse and human bronchial epithelial cells allergic models. Treatment with hucMSC-EVs effectively reduced allergic inflammation, while 146a-EVs showed greater efficacy. The enhanced efficacy in alleviating allergic airway inflammation was attributed to the downregulation of interleukin-1 receptor-associated kinase 1 (IRAK1) and tumor necrosis factor receptor-associated factor 6 (TRAF6) expression, facilitated by miR-146a-5p. This downregulation subsequently led to a decrease in NF-κB nuclear translocation, which in turn resulted in reduced activation of the NLRP3 inflammasome and diminished production of inflammatory cytokines, including IL-6, TNF-α, pro-IL1β and pro-IL18. These findings highlight the potential of miR-146a-5p-engineered hucMSC-derived EVs as a cell-free therapeutic approach for D. farinae-induced allergic airway epithelial cell inflammation.