Date: Sunday, June 12, 2016
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Halls C&D
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 investigated whether microRNA let-7i regulates DCs maturation targeting IL-10 via JAK1-STAT3 signal pathway subsequently prolongs rat cardiac allograft survival.
Methods: QRT-PCR, ELISA, dual-luciferase assay were performed to verify whether IL-10 was the target of let-7i, and regulatory T cells were assessed by flow cytometry and immunohistochemical study, western bolt were performed to detect JAK1, STAT3 and pSTAT3 expression. Lewis recipients of DA heart were transfused with PBS, LPS-mDCs, or let-7i-inhibitor-mDCs. Allograft survival times were recorded, and histologic studies were performed.
Result: Expression of IL-10 mRNA level and production of IL-10 were increased in let-7i-inhibitor-mDCs as compared to LPS-mDCs. Luciferase activity showed that the translational level of the IL-10 luciferase reporter was decreased by let-7i-mimic, but increased by let-7i-inhibitor. MicroRNA let-7i-inhibitor suppressed DC maturation, however, pretreatment of IL-10 SiRNA attenuated the suppression. Expression of JAK1, STAT3, and pSTAT3 in mDCs were suppressed by let-7i-mimic and pretreatment of IL-10 SiRNA, however up-regulated by let-7i-inhibitor. Lewis recipients transfused with let-7i-inhibitor-mDCs significantly prolonged DA cardiac allograft survival. The allografts transfused with let-7i-inhibitor-mDCs showed slight cell infiltration and significantly preserved graft structure. Inhibition of let-7i increased CD4+CD25+Foxp3+ Tregs and modulated cytokine profiles both in vivo and in vitro.
Conclusion: MicroRNA let-7i regulated DCs maturation and function targeting the IL-10 through JAK1-STAT3 pathway. Moreover, transfusion of LPS-induced mDCs transfected with let-7i-inhibitor induced prolonged cardiac allograft survival and generated regulatory T cells.
CITATION INFORMATION: Jin X, Sun Y, Liu X, Wang J, Xu S, Yao L, Zhao Z, Jiang L, Wu Q, Wu J. MicroRNA let-7i Regulates Dendritic Cells Maturation Targeting Interleukin-10 via JAK1-STAT3 Signal Pathway Subsequently Induces Prolonged Cardiac Allograft Survival in Rats. Am J Transplant. 2016;16 (suppl 3).
To cite this abstract in AMA style:Jin X, Sun Y, Liu X, Wang J, Xu S, Yao L, Zhao Z, Jiang L, Wu Q, Wu J. MicroRNA let-7i Regulates Dendritic Cells Maturation Targeting Interleukin-10 via JAK1-STAT3 Signal Pathway Subsequently Induces Prolonged Cardiac Allograft Survival in Rats. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/microrna-let-7i-regulates-dendritic-cells-maturation-targeting-interleukin-10-via-jak1-stat3-signal-pathway-subsequently-induces-prolonged-cardiac-allograft-survival-in-rats/. Accessed April 9, 2020.
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