Date: Monday, May 4, 2015
Session Name: Concurrent Session: Immune Regulation and Graft Survival
Session Time: 4:00pm-5:30pm
Presentation Time: 5:00pm-5:12pm
Location: Room 119-B
Background: Our previous study demonstrated that microRNA (MiR) let-7i could regulate dendritic cells (DCs) maturation and functional state via targeting SOCS1. In this study, we provided evidences suggesting that MiR let-7i targeting IL-10 via JAK1-STAT3 signal pathway regulated DCs maturation subsequently induced cardiac allograft tolerance.
Methods: QRT-PCR, ELISA, dual-luciferase assay were performed to verify whether IL-10 was the target of MiR let-7i, and regulatory T cells were assessed by flow cytometry, western bolt were performed to detect JAK1-STAT3 expression. In vivo, Lewis rats underwent transplantation of a DA heart were adoptively transfused with PBS, LPS-mDCs, or MiR let-7i inhibitor-mDCs for one time, and allograft survival times were recorded by palpation. Acute cellular rejection of cardiac allograft was assessed by histologic study.
Result: The expression of IL-10 mRNA levels and productions of IL-10 in DCs were increased in MiR let-7i inhibitor group compared to LPS group. Luciferase activity showed that the translational level of the IL-10 luciferase reporter was decreased by MiR let-7i mimic, but increased by MiR let-7i inhibitor. MiR let-7i inhibitor suppressed DC maturation by depressing CD80 and CD86, however, pretreatment of IL-10 SiRNA attenuated the suppressed effect. The expressions of JAK1-STAT3 proteins were decreased by MiR let-7i mimic, whereas increased by MiR let-7i inhibitor. Moreover, pretreatment of IL-10 SiRNA decreased JAK1-STAT3 protein expression. Lewis recipients adoptively transfused with MiR let-7i inhibitor-mDC had significantly prolonged DA cardiac allograft survival. The allografts transfected with MiR let-7i inhibitor-mDC showed slight cell infiltration and significantly preserved graft structure. Inhibition of MiR let-7i increased CD4+CD25+Foxp3+ Tregs and modulated cytokine profiles both in vivo and in vitro.
Conclusion: MiR let-7i regulated DCs maturation and functional state targeting the IL-10 through JAK1-STAT3 pathway. Moreover, adoptive transfusion of LPS-induced mDCs transfected with MiR let-7i inhibitor induced cardiac allograft tolerance in our model.
To cite this abstract in AMA style:Wu J, Jin X, Sun Y, Liu X, Chi D, Yu B. MicroRNA let-7i Targeting IL-10 Via JAK1-STAT3 Signal Pathway Regulates Dendritic Cells Maturation Subsequently Induces Cardiac Allograft Tolerance [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/microrna-let-7i-targeting-il-10-via-jak1-stat3-signal-pathway-regulates-dendritic-cells-maturation-subsequently-induces-cardiac-allograft-tolerance/. Accessed April 9, 2020.
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