Bone marrow Tregs mediate stromal cell function and support hematopoiesis via IL-10.

JCI Insight
Virginia CamachoRobert S Welner

Abstract

The nonimmune roles of Tregs have been described in various tissues, including the BM. In this study, we comprehensively phenotyped marrow Tregs, elucidating their key features and tissue-specific functions. We show that marrow Tregs are migratory and home back to the marrow. For trafficking, marrow Tregs use S1P gradients, and disruption of this axis allows for specific targeting of the marrow Treg pool. Following Treg depletion, the function and phenotype of both mesenchymal stromal cells (MSCs) and hematopoietic stem cells (HSCs) was impaired. Transplantation also revealed that a Treg-depleted niche has a reduced capacity to support hematopoiesis. Finally, we found that marrow Tregs are high producers of IL-10 and that Treg-secreted IL-10 has direct effects on MSC function. This is the first report to our knowledge revealing that Treg-secreted IL-10 is necessary for stromal cell maintenance, and our work outlines an alternative mechanism by which this cytokine regulates hematopoiesis.

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Citations

Feb 13, 2021·Cells·Hyojeong HanKatherine Y King
Jul 13, 2021·Journal of Clinical Immunology·Daisuke ToyamaShohei Yamamoto
Aug 10, 2021·Blood·Ronjon Chakraverty, Takanori Teshima

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Methods Mentioned

BETA
RNA-seq
scRNA-seq
PCR

Software Mentioned

Partek Flow
FlowJo
GSEA
Partek
STAR aligner
ImageJ
GraphPad Prism
Diva

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