Dendritic cells mediated by small extracellular vesicles derived from MSCs attenuated the ILC2 activity via PGE2 in patients with allergic rhinitis

Authors：Liu, Xiao-Qing; Peng, Ya-Qi; Huang, Long-Xin; Li, Chan-Gu; Kuang, Peng-Peng; Chen, De-Hua; Wu, Zi-Cong; He, Bi-Xin; Zhou, Zhi-Rou; Fu, Qing-Ling^*

Source：Stem Cell Research & Therapy, 2023, 14(1): 180.

DOI：10.1186/s13287-023-03408-2

• Small extracellular vesicles
• Mesenchymal stromal cells
• Dendritic cells
• Group 2 innate lymphoid cells
• Prostaglandin E2
• Allergic rhinitis

BackgroundMesenchymal stromal cells-derived small extracellular vesicles (MSC-sEVs) have recently attracted considerable attention because of their therapeutic potential in various immune diseases. We previously reported that MSC-sEVs could exert immunomodulatory roles in allergic airway inflammation by regulating group 2 innate lymphoid cell (ILC2) and dendritic cell (DC) functions. Therefore, this study aimed to investigate the indirect effects of MSC-sEVs on ILC2s from patients with allergic rhinitis (AR) via DCs.MethodsHere, we isolated sEVs from induced pluripotent stem cells-MSCs using anion-exchange chromatography and mature DCs (mDCs) were treated with MSC-sEVs. sEV-mDCs were co-cultured with peripheral blood mononuclear cells from patients with AR or purified ILC2s. The levels of IL-13 and GATA3 in ILC2s were examined by flow cytometry. Bulk RNA sequence for mDCs and sEV-mDCs was employed to further probe the potential mechanisms, which were then validated in the co-culture systems.ResultssEV-mDCs showed impaired capacity in priming the levels of IL-13 and GATA3 in ILC2s when compared with mDCs. Furthermore, there was higher PGE2 and IL-10 production from sEV-mDCs, and the blockade of them especially the former one reversed the inhibitory effects of sEV-mDCs.ConclusionsWe demonstrated that MSC-sEVs were able to dampen the activating effects of mDCs on ILC2s in patients with AR. Mechanismly, the PGE2-EP2/4 axis played an essential role in the immunomodulatory effects of sEV-mDCs on ILC2s. Herein, we provided new insights into the mechanism underlying the therapeutic effects of MSC-sEVs in allergic airway inflammation.

• Institution
  南方医科大学; 1; 广东省人民医院; 中山大学