MicroRNA let-7i Targeting IL-10 Via JAK1-STAT3 Signal Pathway Regulates Dendritic Cells Maturation Subsequently Induces Cardiac Allograft Tolerance
1Thoracic Surgery, The Third Affiliated Hospital of Harbin Medical University, Harbin, China
2Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, China
3Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Meeting: 2015 American Transplant Congress
Abstract number: 281
Keywords: Heart/lung transplantation, Rat, Tolerance
Session Information
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.« Back to 2015 American Transplant Congress