CD11c⁺ cells partially mediate the renoprotective effect induced by bone marrow-derived mesenchymal stem cells.
Previous studies have shown that induction of immune tolerance by mesenchymal stem cells (MSCs) is partially mediated via monocytes or dendritic cells (DCs). The purpose of this study was to determine the role of CD11c⁺ cells in MSC-induced effects on ischemia/reperfusion injury (IRI). IRI was induced in wildtype (WT) mice and CD11c⁺-depleted mice following pretreatment with or without MSCs. In the in-vitro experiments, the MSC-treated CD11c⁺ cells acquired regulatory phenotype with increased intracellular IL-10 production. Although splenocytes cocultured with MSCs showed reduced T cell proliferation and expansion of CD4⁺FoxP3⁺ regulatory T cells (Tregs), depletion of CD11c⁺ cells was associated with partial loss of MSCs effect on T cells. In in-vivo experiment, MSCs' renoprotective effect was also associated with induction of more immature CD11c⁺ cells and increased FoxP3 expression in I/R kidneys. However all these effects induced by the MSCs were partially abrogated when CD11c⁺ cells were depleted in the CD11c⁺-DTR transgenic mice. In addition, the observation that adoptive transfer of WT CD11c⁺ cells partially restored the beneficial effect of the MSCs, while transferring IL-10 deficient CD11c⁺ cells did not, strongly suggest the important contribution of IL-10 producing CD11c⁺ cells in attenuating kidney injury by MSCs. Our results suggest that the CD11c⁺ cell-Tregs play critical role in mediating renoprotective effect of MSCs.
Department of Internal Medicine, Korea University Anam Hospital, Seoul, Korea.
Myung-Gyu
MG
Kim
Su Hee
SH
Kim
Hyunjin
H
Noh
Yoon Sook
YS
Ko
Hee Young
HY
Lee
Sang-Kyung
SK
Jo
Won Yong
WY
Cho
Hyoung Kyu
HK
Kim
D058186:Acute Kidney Injury / Q000276:immunology / Q000517:prevention & control*; D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology*; D039521:CD11c Antigen / Q000378:metabolism; D002478:Cells, Cultured; D019610:Cytoprotection / Q000276:immunology*; D003713:Dendritic Cells / Q000502:physiology*; D007249:Inflammation / Q000517:prevention & control; D007668:Kidney / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D015427:Reperfusion Injury / Q000276:immunology / Q000517:prevention & control
D039521:CD11c Antigen