Differential Expression of Long Noncoding RNAs During Cardiac Allograft Rejection.
Department of Hepatic Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
Meeting: 2017 American Transplant Congress
Abstract number: 272
Keywords: Rejection, T helper cells, Tolerance
Session Information
Session Name: Concurrent Session: Mechanisms of Allograft Rejection
Session Type: Concurrent Session
Date: Monday, May 1, 2017
Session Time: 2:30pm-4:00pm
Presentation Time: 3:18pm-3:30pm
Location: E352
While transplant rejection is the major restriction in successful long lasting graft survival, induction of sustainable immune tolerance against transplant is one of the major goal in transplantation to enable long term graft survival. Although various mechanisms have been suggested that induce immune tolerance during transplantation, the roles of long noncoding RNAs (LncRNAs), which modulate gene expression and regulate innate and adaptive immune responses, are not clearly understood in transplantation.
METHODS To understand the gene expression and lncRNA profile during transplantation, we performed microarray to profile lncRNA and mRNA of the heart graft and graft-infiltrating lymphocytes (GILs) in allogeneic and syngeneic mouse heart transplantation model. We screened the differentially expressed lncRNAs and mRNAs, and generated the network of lncRNA-mRNA co-expression. We further validated the selected T cell related lncRNAs by qPCR, which we identified in GSEA analysis. The functional validation of these lncRNAs in the regulation of Th1 response in transplantation was performed by shRNA-mediated inhibition.
RESULTS:
We established a profile of lncRNA and mRNA, which are differentially expressed during transplant rejection in mouse model of heart transplant. Consistent with the microarray results, we have confirmed and validated the expression of seven lncRNA by qPCR. The lncRNA-A930015D03Rik and mouselincRNA1055 were highly expressed in allogeneic heart graft and graft-infiltrating lymphocytes. We further identified that expression of IL-12Rb1 is strongly correlated with lncRNA-A930015D03Rik and mouselincRNA1055 in graft-infiltrating lymphocytes. Further analysis revealed the association of lncRNA-A930015D03Rik and mouselincRNA1055 with Th1 cells in graft rejection. The functions of lncRNA-A930015D03Rik and mouselincRNA1055 were validated in differentiation of Th1 cells by knocking down their expression. Inhibition of lncRNA-A930015D03Rik and mouselincRNA1055 substantially suppressed the expression of IL-12Rβ1 and IFN-g induction in Th1 cells.
CONCLUSIONS: Our results provide a detailed profile of lncRNAs that may regulate immune response and graft outcomes. Our data not only suggests the involvement of lncRNA-A930015D03Rik and mouselincRNA1055 in the regulation of Th1 cells response during graft rejection but also identify them as novel biomarker for sub-clinical graft rejection.
CITATION INFORMATION: Gu G, Hang H, Lu T, Xia Q. Differential Expression of Long Noncoding RNAs During Cardiac Allograft Rejection. Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:
Gu G, Hang H, Lu T, Xia Q. Differential Expression of Long Noncoding RNAs During Cardiac Allograft Rejection. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/differential-expression-of-long-noncoding-rnas-during-cardiac-allograft-rejection/. Accessed May 25, 2025.« Back to 2017 American Transplant Congress