Bone marrow Tregs mediate stromal cell function and support hematopoiesis via IL-10
Male
0301 basic medicine
Immunology
610
Bone Marrow Cells
Cell Communication
T-Lymphocytes, Regulatory
Mice
03 medical and health sciences
Animals
Cells, Cultured
Cell Proliferation
R
600
Mesenchymal Stem Cells
Hematology
Hematopoietic Stem Cells
Coculture Techniques
Hematopoiesis
Interleukin-10
Mice, Inbred C57BL
Medicine
Female
Stromal Cells
Research Article
DOI:
10.1172/jci.insight.135681
Publication Date:
2020-11-18T16:02:14Z
AUTHORS (15)
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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