Research Paper|Volume 11, Issue 20|pp 8911—8924

Immature dendritic cells derived exosomes promotes immune tolerance by regulating T cell differentiation in renal transplantation

Xin-Lu Pang¹, Zhi-Gang Wang¹, Lei Liu¹, Yong-Hua Feng¹, Jun-Xiang Wang¹, Hong-Chang Xie¹, Xian-Lei Yang¹, Jin-Feng Li¹, Gui-Wen Feng¹

¹Department of Kidney Transplantation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China

* Equal contribution

Received: March 7, 2019Accepted: September 27, 2019Published: October 26, 2019

https://doi.org/10.18632/aging.102346

Copyright © 2019 Pang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Objective: To investigate the mechanism of immature dendritic cells-derived exosomes (imDECs) in the regulation of T cell differentiation and immune tolerance in renal allograft model mice.

Results: imDECs significantly improved the percent of survival, relieved inflammatory response, and reduced CD4+T cell infiltration. In addition, imDECs reduced the rejection associated cytokines in allograft mice, and increased the percentage of Foxp3+CD4+T cells in spleen and kidney tissues. imDECs suppressed the IL17+CD4+T cells and promoted the Foxp3+CD4+T cells under Th17 polarization condition. Moreover, miR-682 was found to be highly expressed in imDECs which suppressed the IL17+CD4+T cells and promoted the Foxp3+CD4+T cells. Luciferase reporter assay showed ROCK2 was a target of miR-682, and ROCK mRNA level was negative correlated with miR-682 mRNA level.

Conclusion: miR-682 was highly expressed in imDECs, and imDECs-secreted miR-682 promoted Treg cell differentiation by negatively regulating ROCK2 to promote immune tolerance in renal allograft model mice.

Methods: Renal allograft model mice were established, and imDECs or mature dendritic cells-derived exosomes (mDECs) were injected into model mice. Rejection associated cytokines IFN-γ, IL-2, IL-17 levels in plasma were detected by ELISA. IL-17A, Foxp3, miR-682, ROCK2, p-STAT3, p-STAT5 expressions were measured by qRT-PCR or western blot.