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Analysis of Pulmonary Dendritic Cell Maturation and Migration during Allergic Airway Inflammation
Published on: July 23, 2012
Dendritic cells mediated by small extracellular vesicles derived from MSCs attenuated the ILC2 activity via PGE2 in
Xiao-Qing Liu1,2, Ya-Qi Peng3, Long-Xin Huang1,2
1Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road II, Guangzhou, 510080, Guangdong, People's Republic of China.
Background:
Mesenchymal 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.
Methods:
Here, 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.
Results:
sEV-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.
Conclusions:
We 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.
Insights
Mesenchymal stromal cell-derived small extracellular vesicles (MSC-sEVs) dampen allergic rhinitis by inhibiting dendritic cell activation of innate lymphoid cells. The PGE2-EP2/4 axis is key to this immunomodulatory effect.
Area of Science:
- Immunology
- Cell Biology
- Extracellular Vesicles
Background:
- Mesenchymal stromal cells-derived small extracellular vesicles (MSC-sEVs) show therapeutic potential for immune diseases.
- Previous work demonstrated MSC-sEVs modulate group 2 innate lymphoid cells (ILC2s) and dendritic cells (DCs) in allergic airway inflammation.
- This study investigates the indirect impact of MSC-sEVs on ILC2s from allergic rhinitis (AR) patients via DCs.
Purpose of the Study:
- To elucidate the indirect immunomodulatory effects of MSC-sEVs on ILC2s from AR patients through DCs.
- To identify the underlying molecular mechanisms of MSC-sEVs' action on DC-ILC2 interactions.
Main Methods:
- Small extracellular vesicles (sEVs) were isolated from MSCs.
- Dendritic cells (DCs) were treated with MSC-sEVs (resulting in sEV-mDCs).
- sEV-mDCs were co-cultured with AR patient PBMCs or purified ILC2s; IL-13 and GATA3 levels were assessed via flow cytometry; bulk RNA sequencing was performed on DCs and sEV-mDCs.
Main Results:
- sEV-mDCs exhibited a reduced capacity to prime IL-13 and GATA3 levels in ILC2s compared to control mDCs.
- sEV-mDCs produced higher levels of PGE2 and IL-10.
- Blocking PGE2, in particular, reversed the inhibitory effects of sEV-mDCs on ILC2s.
Conclusions:
- MSC-sEVs effectively dampen DC activation of ILC2s in allergic rhinitis.
- The PGE2-EP2/4 axis is crucial for the immunomodulatory effects of sEV-mDCs on ILC2s.
- These findings offer new insights into the therapeutic mechanisms of MSC-sEVs for allergic airway inflammation.
