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Small extracellular vesicles derived from human mesenchymal stem cells prevent Th17-dominant neutrophilic airway inflammation via immunoregulation on Th17 cells.
- Source :
-
International immunopharmacology [Int Immunopharmacol] 2024 May 30; Vol. 133, pp. 112126. Date of Electronic Publication: 2024 Apr 25. - Publication Year :
- 2024
-
Abstract
- Type 17 helper T cells (Th17)-dominant neutrophilic airway inflammation is critical in the pathogenesis of steroid-resistant airway inflammation such as severe asthma. Small extracellular vesicles (sEV) derived from human mesenchymal stem cells (MSCs) display extensive therapeutic effects and advantages in many diseases. However, the role of MSC-sEV in Th17-dominant neutrophilic airway inflammation and the related mechanisms are still poorly studied. Here we found that MSC-sEV significantly alleviated the infiltration of inflammatory cells in peribronchial interstitial tissues and reduced levels of inflammatory cells, especially neutrophils, in bronchoalveolar lavage fluids (BALF) of mice with neutrophilic airway inflammation. Consistently, MSC-sEV significantly decreased levels of IL-17A in BALF and Th17 in lung tissues. Furthermore, we found that labelled MSC-sEV were taken up by human CD4 <superscript>+</superscript> T cells most obviously at 12 h after incubation, and distributed mostly in mouse lungs. More importantly, potential signaling pathways involved in the MSC-sEV mediated inhibition of Th17 polarization were found using RNA sequencing. Using Western blot, JAK2-STAT3 pathway was identified as an important role in the inhibition of Th17 polarization by MSC-sEV. We found that proteins in MSC-sEV were mostly involved in the therapeutic effects of MSC-sEV. In total, our study suggested that MSC-sEV could be a potential therapeutic strategy for the treatment of neutrophilic airway inflammation.<br /> (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
- Subjects :
- Humans
Animals
Mice
Janus Kinase 2 metabolism
Interleukin-17 metabolism
Lung immunology
Lung pathology
Mice, Inbred C57BL
Cells, Cultured
Bronchoalveolar Lavage Fluid immunology
Bronchoalveolar Lavage Fluid cytology
Asthma immunology
Asthma therapy
Male
Signal Transduction
Female
Disease Models, Animal
Th17 Cells immunology
Extracellular Vesicles metabolism
Extracellular Vesicles immunology
Mesenchymal Stem Cells immunology
Mesenchymal Stem Cells metabolism
Neutrophils immunology
STAT3 Transcription Factor metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1878-1705
- Volume :
- 133
- Database :
- MEDLINE
- Journal :
- International immunopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 38669946
- Full Text :
- https://doi.org/10.1016/j.intimp.2024.112126