| First Author | Huang Y | Year | 2018 |
| Journal | Stem Cells | Volume | 36 |
| Issue | 10 | Pages | 1567-1577 |
| PubMed ID | 30004616 | Mgi Jnum | J:268868 |
| Mgi Id | MGI:6269599 | Doi | 10.1002/stem.2887 |
| Citation | Huang Y, et al. (2018) Fms-Like Tyrosine Kinase 3-Ligand Contributes to the Development and Function of the Subpopulation of CD8alpha(+) Plasmacytoid Precursor Dendritic Cells in CD8(+) /TCR(-) Facilitating Cells. Stem Cells 36(10):1567-1577 |
| abstractText | Facilitating cells (FC) are a CD8(+) TCR(-) bone marrow subpopulation that enhance engraftment of purified hematopoietic stem cells (HSC) and induce antigen-specific CD4(+) CD25(+) FoxP3(+) regulatory T cell (Treg) in vivo. The major subpopulation in FC resembles plasmacytoid precursor dendritic cells (p-preDC) both phenotypically and functionally. Here, we report that the number of FC was significantly reduced in Fms-like tyrosine kinase 3-ligand-knockout (Flt3-L-KO) mice. Specifically, there was a selective decrease in the B220(+) CD11c(+) CD11b(-) p-preDC FC subpopulation. The p-preDC FC subpopulation in FC total is restored after Flt3-L administration to Flt3-L-KO mice. FC from Flt3-L-KO donors exhibit impaired facilitation of allogeneic HSC engraftment in ablatively conditioned mice (B6 --> NOD) as well as in mice conditioned with reduced intensity conditioning (B6 --> BALB/c). In addition, the number of CD4(+) CD25(+) Foxp3(+) Treg from Flt3-L-KO mice is significantly decreased. This was associated with the expression of chemokine receptor CXCR3(+) or CCR5(+) on Treg. Treg from the spleen of Flt3-L-KO mice showed impaired facilitation of engraftment of allogeneic HSC compared to wild-type Treg. Flt3-L treatment significantly expanded Treg, and restored their facilitating function. These results suggest that Flt3-L is an important growth factor in the development and homeostasis of p-preDC FC and in the role of FC inducing generation of Treg. Flt3-L provides potent immunoregulatory properties that may be clinically useful to improve tolerance induction and enhance the function of allogeneic cell therapies. Stem Cells 2018;36:1567-1577. |
