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  • 제22권5호
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  • Pages.40.1-40.24
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  • 2022
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  • 1598-2629(pISSN)
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  • 2092-6685(eISSN)
대한면역학회 (The Korean Association of Immunobiologists)
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Mesenchymal Stem Cells Attenuate Asthmatic Inflammation and Airway Remodeling by Modulating Macrophages/Monocytes in the IL-13-Overexpressing Mouse Model

  • Yosep Mo (Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul National University College of Medicine) ;
  • Yujin Kim (Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul National University College of Medicine) ;
  • Ji-Young Bang (Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul National University College of Medicine) ;
  • Jiung Jung (Department of Internal Medicine, Seoul National University Hospital) ;
  • Chun-Geun Lee (Brown University, Molecular Microbiology and Immunology) ;
  • Jack A. Elias (Brown University, Molecular Microbiology and Immunology) ;
  • Hye-Ryun Kang (Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul National University College of Medicine)
  • 투고 : 2022.03.25
  • 심사 : 2022.08.22
  • 발행 : 2022.10.31
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초록

Mesenchymal stem cells (MSCs) are attractive alternatives to conventional anti-asthmatic drugs for severe asthma. Mechanisms underlying the anti-asthmatic effects of MSCs have not yet been elucidated. This study evaluated the anti-asthmatic effects of intravenously administered MSCs, focusing on macrophages and monocytes. Seven-week-old transgenic (Tg) mice with lung-specific overexpression of IL-13 were used to simulate chronic asthma. MSCs were intravenously administered four days before sampling. We examined changes in immune cell subpopulations, gene expression, and histological phenotypes. IL-13 Tg mice exhibited diverse features of chronic asthma, including severe type 2 inflammation, airway fibrosis, and mucus metaplasia. Intravenous administration of MSCs attenuated these asthmatic features just four days after a single treatment. MSC treatment significantly reduced SiglecF-CD11c-CD11b+ monocyte-derived macrophages (MoMs) and inhibited the polarization of MoMs into M2 macrophages, especially M2a and M2c. Furthermore, MSCs downregulated the excessive accumulation of Ly6c- monocytes in the lungs. While an intravenous adoptive transfer of Ly6c- monocytes promoted the infiltration of MoM and Th2 inflammation, that of MSC-exposed Ly6c- monocytes did not. Ex vivo Ly6c- MoMs upregulated M2-related genes, which were reduced by MSC treatment. Molecules secreted by Ly6c- MoMs from IL-13 Tg mice lungs upregulated the expression of fibrosis-related genes in fibroblasts, which were also suppressed by MSC treatment. In conclusion, intravenously administered MSCs attenuate asthma phenotypes of chronic asthma by modulating macrophages. Identifying M2 macrophage subtypes revealed that exposure to MSCs transforms the phenotype and function of macrophages. We suggest that Ly6c- monocytes could be a therapeutic target for asthma management.

키워드

과제정보

This research was supported by the National Research Foundation (NRF) funded by the Korean government (MSIT) (No. NRF-2017M3A9B4061887). Parts of figures were created with BioRender.com. We would like to express our sincere gratitude to Joony Yim for helping us develop the main findings of this study more clearly.

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