#1297

Endometrial Regeneration Cell-derived Exosomes Carrying siCD3 Inhibit Kidney Allograft Rejection through Suppression of α-2,6 Sialylation

Y. Xu¹, H. Wang², X. Zhao³, B. Sun⁴

¹Tianjin Medical University, Tianjin, China
²Tianjin Medical University General Hospital, Tianjin, China
³Tianjin Medical University, Department of Pathology, Tianjin, China
⁴Tianjin Medical University General Hospital, Department of Pathology, Tianjin, China

Introduction:

Kidney transplant rejection is a major component in the poor prognosis of organ transplantation. Due to the multiple complicated mechanisms involved, a novel therapy remains under exploration. Endometrial regenerative cells (ERCs) have been ubiquitously applied to various refractory immune-related diseases, but the role of ERC-derived exosomes (ERC-Exos) in alleviating transplant rejection has not been thoroughly studied. Cluster of differentiation 3 (CD3) plays an important role in regulating immune responses. In this study, we have demonstrated for the first time that ERC-Exo carried with siCD3 attenuated allograft rejection by inhibiting T-cell proliferation and differentiation.

Material and methods:

C57BL/6 mouse recipients receiving bm12 mouse kidney allografts were randomly divided into four groups. Graft pathological changes were evaluated by H&E staining. Splenic immune cell populations were analyzed using flow cytometry. Serum cytokine profiles of recipients were measured by ELISA. The proliferation capacity of CD8+T cell populations was also assessed in vitro. α-2,6-sialylation levels in CD8+T cells were measured by SNA blot.

Results:

In vivo, mice treated with ERC-siCD3 Exos achieved significantly prolonged allograft survival. Serum cytokine profiles of recipients were significantly changed in ERC-siCD3 Exos-treated recipients. In vitro, we found that ERC-siCD3 Exos considerably down-regulated the α-2,6-sialyltransferase (ST6GAL1) expression in CD8+T cells, and significantly reduced α-2,6-sialylation levels. Through desialylation modification, ERC-siCD3 Exo therapy significantly decreased CD8+T cell proliferation and inhibited CD8+T cell differentiation into Th1 and Th17 cells while promoting Treg differentiation.