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Mesenchymal Stem Cells Suppress Severe Asthma by Directly Regulating Th2 Cells and Type 2 Innate Lymphoid Cells

  • Shin, Jae Woo (Laboratory of Mucosal Immunology, Department of Biomedical Sciences, Seoul National University College of Medicine) ;
  • Ryu, Seungwon (Laboratory of Mucosal Immunology, Department of Biomedical Sciences, Seoul National University College of Medicine) ;
  • Ham, Jongho (Laboratory of Mucosal Immunology, Department of Biomedical Sciences, Seoul National University College of Medicine) ;
  • Jung, Keehoon (Department of Anatomy and Cell Biology, Seoul National University College of Medicine) ;
  • Lee, Sangho (Department of Biological Sciences, Sungkyunkwan University) ;
  • Chung, Doo Hyun (Department of Pathology, Seoul National University College of Medicine) ;
  • Kang, Hye-Ryun (Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center) ;
  • Kim, Hye Young (Laboratory of Mucosal Immunology, Department of Biomedical Sciences, Seoul National University College of Medicine)
  • Received : 2021.04.19
  • Accepted : 2021.05.27
  • Published : 2021.08.31

Abstract

Patients with severe asthma have unmet clinical needs for effective and safe therapies. One possibility may be mesenchymal stem cell (MSC) therapy, which can improve asthma in murine models. However, it remains unclear how MSCs exert their beneficial effects in asthma. Here, we examined the effect of human umbilical cord blood-derived MSCs (hUC-MSC) on two mouse models of severe asthma, namely, Alternaria alternata-induced and house dust mite (HDM)/diesel exhaust particle (DEP)-induced asthma. hUC-MSC treatment attenuated lung type 2 (Th2 and type 2 innate lymphoid cell) inflammation in both models. However, these effects were only observed with particular treatment routes and timings. In vitro co-culture showed that hUC-MSC directly downregulated the interleukin (IL)-5 and IL-13 production of differentiated mouse Th2 cells and peripheral blood mononuclear cells from asthma patients. Thus, these results showed that hUC-MSC treatment can ameliorate asthma by suppressing the asthmogenic cytokine production of effector cells. However, the successful clinical application of MSCs in the future is likely to require careful optimization of the route, dosage, and timing.

Keywords

Acknowledgement

This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIT) (No. NRF-2017M3A9B4061887 and SRC 2017R1A5A1014560). The authors would like to express their gratitude to Professor In-Gyu Kim of Seoul National University College of Medicine for providing the hUC-MSCs.

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