The Plasticity of Mesenchymal Stem Cells in Regulating Surface HLA-I

Yafei Wang; Jiayun Huang; Lin Gong; Dongsheng Yu; Chenrui An; Varitsara Bunpetch; Jun Dai; He Huang; Xiaohui Zou; Hongwei Ouyang; Hua Liu

doi:10.1016/j.isci.2019.04.011

The Plasticity of Mesenchymal Stem Cells in Regulating Surface HLA-I

iScience. 2019 May 31:15:66-78. doi: 10.1016/j.isci.2019.04.011. Epub 2019 Apr 11.

Authors

Yafei Wang¹, Jiayun Huang², Lin Gong¹, Dongsheng Yu³, Chenrui An¹, Varitsara Bunpetch¹, Jun Dai⁴, He Huang⁵, Xiaohui Zou⁶, Hongwei Ouyang⁷, Hua Liu⁸

Affiliations

¹ 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.
² 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.
³ Department of Orthopedics, Zhejiang Provincial People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, 310014, P.R.China.
⁴ Department of Medical Genetics, Medicum, University of Helsinki, Helsinki 00290, Finland.
⁵ 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.
⁶ Central Laboratory, the First Affiliated Hospital, Zhejiang University, School of Medicine, Hangzhou, Zhejiang 310003, P.R.China.
⁷ 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.
⁸ 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.

Abstract

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)-γ 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-γ-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.

Keywords: Biological Sciences; Cell Biology; Immunology; Stem Cells Research.