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Mesenchymal stem cells attenuate ischemic acute kidney injury by inducing regulatory T cells through splenocyte interactions.
|Title||Mesenchymal stem cells attenuate ischemic acute kidney injury by inducing regulatory T cells through splenocyte interactions.|
|Publication Type||Journal Article|
|Year of Publication||2013|
|Authors||Hu J, Zhang L, Wang N, Ding R, Cui S, Zhu F, Xie Y, Sun X, Wu D, Hong Q, Li Q, Shi S, Liu X, Chen X|
|Date Published||2013 Sep|
The mechanism of mesenchymal stem cell therapy in acute kidney injury remains uncertain. Previous studies indicated that mesenchymal stem cells could attenuate inflammation-related organ injury by induction of regulatory T cells. Whether regulatory T-cell induction is a potential mechanism of mesenchymal stem cell therapy in ischemic acute kidney injury and how these induced regulatory T cells orchestrate local inflammation are unknown. Here we found that mesenchymal stem cells decrease serum creatinine and urea nitrogen levels, improve tubular injury, and downregulate IFN-γ production of T cells in the ischemic kidney. In addition to the lung, mesenchymal stem cells persisted mostly in the spleen. Mesenchymal stem cells increased the percentage of regulatory T cells in the spleen and the ischemic kidney. Antibody-dependent depletion of regulatory T cells blunted the therapeutic effect of mesenchymal stem cells, while coculture of splenocytes with mesenchymal stem cells caused an increase in the percentage of regulatory T cells. Splenectomy abrogated attenuation of ischemic injury, and downregulated IFN-γ production and the induction of regulatory T cells by mesenchymal stem cells. Thus, mesenchymal stem cells ameliorate ischemic acute kidney injury by inducing regulatory T cells through interactions with splenocytes. Accumulated regulatory T cells in ischemic kidney might be involved in the downregulation of IFN-γ production.
|Alternate Journal||Kidney Int.|