Effect of miR-744 on Ameliorating Heart Allograft Rejection in BALB/c Mice Via Regulation of TNFRSF4 Expression in Regulatory T Cells
CD134 (TNFRSF4) is a member of the TNFR superfamily, which is specifically expressed on T cells. Previous studies have shown that blocking of CD134L-CD134 interaction reduces the percentage of activated T cells and prevents effector T cell–mediated graft rejection in heart transplantation. However,...
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Published in | Transplantation proceedings Vol. 52; no. 1; pp. 398 - 405 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
01.01.2020
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Online Access | Get full text |
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Summary: | CD134 (TNFRSF4) is a member of the TNFR superfamily, which is specifically expressed on T cells. Previous studies have shown that blocking of CD134L-CD134 interaction reduces the percentage of activated T cells and prevents effector T cell–mediated graft rejection in heart transplantation. However, the role of microRNA-regulated inhibition of the CD134 signal in cardiac transplantation of T-regulatory (Treg) cells is not clear. In this study, we found microRNA 744 (miR-744) agomir administration enhanced the expression levels of miR-744 in CD4+CD25+ Treg cells from heart transplantation mice. Moreover, miR-744 agomir administration significantly enhanced the expression levels of CD62L and Ki67 in CD4+CD25+ Treg cells from heart transplantation mice and further enhanced immunosuppressive function of Treg cells following coculture with CD4+CD25- T cells for different ratios. In addition, miR-744 agomir treatment significantly prolonged survival time and reduced rejection response of heart allografts in vivo, which are involved in downregulation of TNFRSF4 expression. These results provided a novel molecular mechanism of ameliorating heart allograft rejection in Treg cells, which could be used in the treatment of heart allograft rejection clinically.
•MicroRNA 744 (miR-744) level was decreased in CD4+CD25+ T-regulatory (Treg) cells following heart transplantation.•miR-744 agomir administration enhanced CD4+CD25+ Treg function.•miR-744 agomir administration prolonged survival of heart allografts in vivo.•miR-744 agomir directly targeted the TNFRSF4 gene. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0041-1345 1873-2623 |
DOI: | 10.1016/j.transproceed.2019.10.014 |