The plasticity of mesenchymal stem cells in regulating surface HLA-I

Abstract

Summary A low surface expression level of human leukocyte antigen class I(HLA-I) ensures 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 IFN-γ treatment, while interestingly, their surface HLA-I expression was downregulated after reaching an HLA-I surface expression peak. Microarray data indicated the post-transcriptional process plays an important role in 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, the cells which 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.