Sca-1+Lin−CD117− Mesenchymal Stem/Stromal Cells Induce the Generation of Novel IRF8-Controlled Regulatory Dendritic Cells through Notch–RBP-J Signaling

Xingxia Liu, Shaoda Ren, Chaozhuo Ge, Kai Cheng, Martin Zenke, Armand Keating, Robert C H Zhao
J Immunol 2015 May 30;194(9):4298-308. Epub 2015 Mar 30.

Mesenchymal stem/stromal cells (MSCs) can influence the destiny of hematopoietic stem/progenitor cells (HSCs) and exert broadly immunomodulatory effects on immune cells. However, how MSCs regulate the differentiation of regulatory dendritic cells (regDCs) from HSCs remains incompletely understood. In this study, we show that mouse bone marrow–derived Sca-1+Lin−CD117− MSCs can drive HSCs to differentiate into a novel IFN regulatory factor (IRF)8–controlled regDC population (Sca+ BM-MSC–driven DC [sBM-DCs]) when cocultured without exogenous cytokines. The Notch pathway plays a critical role in the generation of the sBM-DCs by controlling IRF8 expression in an RBP-J–dependent way…