PMID- 31030183 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200928 IS - 2589-0042 (Electronic) IS - 2589-0042 (Linking) VI - 15 DP - 2019 May 31 TI - The Plasticity of Mesenchymal Stem Cells in Regulating Surface HLA-I. PG - 66-78 LID - S2589-0042(19)30108-7 [pii] LID - 10.1016/j.isci.2019.04.011 [doi] AB - A low surface expression level of human leukocyte antigen class I (HLA-I) ensures that the mesenchymal stem cells (MSCs) escape from the allogeneic recipients' immunological surveillance. Here, we discovered that both transcriptional and synthesis levels of HLA-I in MSCs increased continuously after interferon (IFN)-gamma treatment, whereas interestingly, their surface HLA-I expression was downregulated after reaching an HLA-I surface expression peak. Microarray data indicated that the post-transcriptional process plays an important role in the downregulation of surface HLA-I. Further studies identified that IFN-gamma-treated MSCs accelerated HLA-I endocytosis through a clathrin-independent dynamin-dependent endocytosis pathway. Furthermore, cells that have self-downregulated surface HLA-I expression elicit a weaker immune response than they previously could. Thus uncovering the plasticity of MSCs in the regulation of HLA-I surface expression would reveal insights into the membrane transportation events leading to the maintenance of low surface HLA-I expression, providing more evidence for selecting and optimizing low-immunogenic MSCs to improve the therapeutic efficiency. CI - Copyright (c) 2019 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Wang, Yafei AU - Wang Y AD - Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, School of Medicine, Hangzhou 310058, P.R.China; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Zhejiang University, School of Medicine, Hangzhou 310058, P.R.China. FAU - Huang, Jiayun AU - Huang J AD - Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, School of Medicine, Hangzhou 310058, P.R.China; Department of Orthopedic Surgery, 2nd Affiliated Hospital, Zhejiang University, School of Medicine, Zhejiang 310009, P.R.China; Orthopaedics Research Institute of Zhejiang University, Zhejiang 310009, P.R.China. FAU - Gong, Lin AU - Gong L AD - Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, School of Medicine, Hangzhou 310058, P.R.China; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Zhejiang University, School of Medicine, Hangzhou 310058, P.R.China. FAU - Yu, Dongsheng AU - Yu D AD - Department of Orthopedics, Zhejiang Provincial People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, 310014, P.R.China. FAU - An, Chenrui AU - An C AD - Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, School of Medicine, Hangzhou 310058, P.R.China; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Zhejiang University, School of Medicine, Hangzhou 310058, P.R.China. FAU - Bunpetch, Varitsara AU - Bunpetch V AD - Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, School of Medicine, Hangzhou 310058, P.R.China; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Zhejiang University, School of Medicine, Hangzhou 310058, P.R.China. FAU - Dai, Jun AU - Dai J AD - Department of Medical Genetics, Medicum, University of Helsinki, Helsinki 00290, Finland. FAU - Huang, He AU - Huang H AD - Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University, School of Medicine, Hangzhou, Zhejiang 310003, P.R. China; Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang 310003, P.R.China. FAU - Zou, Xiaohui AU - Zou X AD - Central Laboratory, the First Affiliated Hospital, Zhejiang University, School of Medicine, Hangzhou, Zhejiang 310003, P.R.China. FAU - Ouyang, Hongwei AU - Ouyang H AD - Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, School of Medicine, Hangzhou 310058, P.R.China; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Zhejiang University, School of Medicine, Hangzhou 310058, P.R.China; Department of Sports Medicine, Zhejiang University, School of Medicine, Hangzhou 310058, P.R.China; Zhejiang University-University of Edinburgh Institute & School of Basic Medicine, Zhejiang University, School of Medicine, Hangzhou 310003, P. R. China; China Orthopedic Regenerative Medicine Group (CORMed), Hangzhou 310003, P.R. China. FAU - Liu, Hua AU - Liu H AD - Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, School of Medicine, Hangzhou 310058, P.R.China; Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Zhejiang University, School of Medicine, Hangzhou 310058, P.R.China. Electronic address: liuhua@zju.edu.cn. LA - eng PT - Journal Article DEP - 20190411 PL - United States TA - iScience JT - iScience JID - 101724038 PMC - PMC6487373 OTO - NOTNLM OT - Biological Sciences OT - Cell Biology OT - Immunology OT - Stem Cells Research EDAT- 2019/04/29 06:00 MHDA- 2019/04/29 06:01 PMCR- 2019/04/11 CRDT- 2019/04/29 06:00 PHST- 2018/10/23 00:00 [received] PHST- 2019/02/27 00:00 [revised] PHST- 2019/04/06 00:00 [accepted] PHST- 2019/04/29 06:00 [pubmed] PHST- 2019/04/29 06:01 [medline] PHST- 2019/04/29 06:00 [entrez] PHST- 2019/04/11 00:00 [pmc-release] AID - S2589-0042(19)30108-7 [pii] AID - 10.1016/j.isci.2019.04.011 [doi] PST - ppublish SO - iScience. 2019 May 31;15:66-78. doi: 10.1016/j.isci.2019.04.011. Epub 2019 Apr 11.