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CD39-mediated effect of human bone marrow-derived mesenchymal stem cells on the human Th17 cell function
Authors:Jong Joo Lee  Hyun Jeong Jeong  Mee Kum Kim  Won Ryang Wee  Won Woo Lee  Seung U Kim  Changmin Sung  Yung Hun Yang
Institution:1. Department of Ophthalmology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799, South Korea
2. Laboratory of Ocular Regenerative Medicine and Immunology, Seoul Artificial Eye Center, Seoul National University Hospital Biomedical Research Institute, Seoul, South Korea
3. Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, South Korea
4. Medical Research Institute, Chung-Ang University College of Medicine, Seoul, South Korea
5. Division of Neurology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada
6. Interdisciplinary Program of Bioengineering, Seoul National University, Seoul, South Korea
7. Department of Microbial Engineering, College of Engineering, Konkuk University, Seoul, South Korea
Abstract:This study investigated the immune-modulatory effects of human bone marrow-derived mesenchymal stem cells (hBMSCs) on human Th17 cell function through the CD39-mediated adenosine-producing pathway. The suppressive effects of hBMSCs were evaluated by assessing their effects on the proliferation of Th17 cells and the secretion of interferon (IFN)-γ and interleukin (IL)-17A by Th17 cells with or without anti-CD39 treatment. Changes in CD39 and CD73 expression on the T cells with or without co-culture of hBMSCs were evaluated by flow cytometry. hBMSCs effectively suppressed the proliferation of Th17 cells and the secretion of both IL-17A and IFN-γ from Th17 cells using by both flow cytometry and ELISA, while anti-CD39 treatment significantly reduced the inhibitory effects of hBMSCs on the proliferation and secretion of the Th17 cells. The hBMSCs induced increased expression of the CD39 and CD73 on T cells correlated with the suppressive function of hBMSCs, which was accompanied by increased adenosine production. Our data suggests that hBMSCs can effectively suppress immune responses of the Th17 cells via the CD39-CD73-mediated adenosine-producing pathway.
Keywords:Bone marrow-derived mesenchymal stem cells  Th17 cells  CD39  CD73  Interleukin-17  Interferon-γ  Adenosine
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