Abstract

our data are consistent with the BM and not splenic microenvironment is, at least in part, driving this BM-Treg signature, as adoptively transferred splenic Treg that entered the BM niche acquired a BM-Treg phenotype. Analyses identified upregulated expression of IL-9R, IL-33R, and IL-7R in BM-Treg. Administration of the T cell produced cytokine IL-2 was required by splenic Treg expansion but had no impact on BM-Treg, whereas the converse was true for IL-9 administration. Plasmacytoid dendritic cells (pDCs) within the BM also may contribute to BM-Treg maintenance. Using pDC-specific BDCA2-DTR mice in which diptheria toxin administration results in global pDC depletion, we demonstrate that pDC depletion hampers BM, but not splenic, Treg 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.

Authors	Nicholls, Jemma; Cao, Benjamin; Le Texier, Laetitia; Xiong, Laura Yan; Hunter, Christopher R; Llanes, Genesis; Aguliar, Ethan G; Schroder, Wayne A; Phipps, Simon; Lynch, Jason P; Cao, Huimin; Heazlewood, Shen Y; Williams, Brenda; Clouston, Andrew D; Nefzger, Christian M; Polo, Jose M; Nilsson, Susan K; Blazar, Bruce R; MacDonald, Kelli P A
Journal	Frontiers in cell and developmental biology
Pages	737880
Volume	9
Date	1/01/2021
Grant ID
Funding Body
URL	http://www.ncbi.nlm.nih.gov/pubmed/?term=10.3389/fcell.2021.737880