Key Points
• Conclusion/Relevance: “Using pDC-specific BDCA2-DTR mice in which diptheria toxin administration results in global pDC [plasmacytoid dendritic cells] depletion, we demonstrate that pDC depletion hampers BM [bone marrow], but not splenic, Treg [Regulatory T cell] homeostasis. Together, these data provide evidence that BM-Treg and splenic Treg are phenotypically and functionally distinct and influenced by niche-specific mediators that selectively support their respective Treg populations. The unique properties of BM-Treg should be considered for new therapies to reconstitute Treg and reestablish tolerance following SCT [stem cell transplantation].”
• The authors showed that while BM niche is a rich source of Treg post-SCT, these Treg don’t reconstitute during GVHD. BM Treg contribute a functional role in controlling GVHD and restricted depletion of BM-Tre boosted disease severity in mouse models, despite maintaining splenic Treg.
• Unlike previous researchers, the researchers in the current study found that BM-Treg was more quiescent/less functional vs pTreg. The BM-Treg quiescent state was associated with the downregulated expression of several genes usually linked to optimal Treg-mediated suppression, such as FoxP3, Ki67, and GARP. This phenomenon was mirrored in a decrease of in vitro suppressive function vs splenic Treg.
• “Our data suggest that the BM niche is acting as a biological resting site for pTreg by supporting the survival of long-lived memory Treg, while allowing them to retain distinct elements of their highly functional Treg signatures,” wrote the authors.