MicroRNA let-7i Regulates Dendritic Cells Maturation Targeting Interleukin-10 via JAK1-STAT3 Signal Pathway Subsequently Induces Prolonged Cardiac Allograft Survival in Rats.
1Thoracic Surgery, The Third Affiliated Hospital of Harbin Medical University, Harbin, China
2Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
3Pediatric Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
4Otorhinolaryngology, The First Affiliated Hospital of Harbin Medical University, Harbin, China
5Ophthalmology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Meeting: 2016 American Transplant Congress
Abstract number: B24
Keywords: Heart/lung transplantation, Rat, Tolerance
Session Information
Session Name: Poster Session B: Allograft Rejection, Tolerance, and Xenotransplantation
Session Type: Poster Session
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 May 9, 2025.« Back to 2016 American Transplant Congress