Fms-Like Tyrosine Kinase 3-Ligand Contributes to the Development and Function of the Subpopulation of CD8α+ Plasmacytoid Precursor Dendritic Cells in CD8+ /TCR- Facilitating Cells

Stem Cells
Yiming HuangSuzanne T Ildstad

Abstract

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 restore...Continue Reading

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Citations

Jun 4, 2020·Clinical & Translational Immunology·Yishan YeFlorent Malard

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