Exosomes Secreted by Mesenchymal Stem Cells Induce Immune Tolerance to Mouse Kidney Transplantation via Transporting LncRNA DANCR

Mesenchymal stem cells induce kidney transplant tolerance by increasing regulatory T (Treg) cells. Bone marrow mesenchymal stem cell exosomes (BM MSC-Ex) promote Treg cell differentiation. Long non-coding RNA differentiation antagonizing non-protein coding RNA (DANCR) is expressed in BMMSCs and can be encapsulated in exosomes. We aimed to explore the role of DANCR in BM MSC-Ex in immune tolerance after kidney transplantation and related mechanism. The isogenic/allograft kidney transplantation mouse model was established, and levels of serum creatinine (SCr) were determined. Hematoxylin-eosin staining was conducted to detect the inflammation, and immunohistochemistry was performed to detect the infiltration of CD4(+) T cells. Levels of IFN-gamma, IL-17, and IL-2 were examined by ELISA. Flow cytometry was conducted to determine Treg cells. In the allograft group, the inflammatory response was severe, CD4(+) T cell infiltration, SCr levels, and plasma rejection-related factors were up-regulated, while injection of BM MSC-Ex reversed the results. BM MSC-Ex increased Treg cells in kidney transplantation mice. Interference with DANCR reversed the promoting effect of BM MSC-Ex on Treg cell differentiation. DANCR bound to SIRT1, promoted ubiquitination and accelerated its degradation. The injection of BM MSC-Ex (after interference with DANCR) promoted SIRT1 levels, inflammatory response, CD4(+) T cell infiltration, SCr levels, and plasma rejection related factors' expression, while Treg cells were decreased. LncRNA DANCR in BM MSC-Ex promoted Treg cell differentiation and induced immune tolerance of kidney transplantation by down-regulating SIRT1 expression in CD4(+) T cells.

Automated summary

The study revealed that DANCR in BM MSC-Ex promotes Treg cell differentiation and induces immune tolerance of kidney transplantation by down-regulating SIRT1 expression in CD4(+) T cells.