Bone marrow Tregs mediate stromal cell function and support hematopoiesis via IL-10
| Autor: | Sweta B. Patel, Emma C. Dean, Ashley E. Landuyt, Henry Yang, Victoria R. Matkins, Craig L. Maynard, Jeremie M. Lever, Li Ying, James F. George, Paul Brent Ferrell, Virginia Camacho, Robert S. Welner, Casey T. Weaver, Heth R. Turnquist, Zhengqin Yang |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Stromal cell medicine.medical_treatment Immunology T cells Bone Marrow Cells chemical and pharmacologic phenomena Cell Communication Biology T-Lymphocytes Regulatory Mice 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Animals Bone marrow Cells Cultured Cell Proliferation Hematology Mesenchymal stem cell Mesenchymal Stem Cells hemic and immune systems General Medicine Hematopoietic Stem Cells Coculture Techniques Hematopoiesis Interleukin-10 Mice Inbred C57BL Transplantation Haematopoiesis 030104 developmental biology medicine.anatomical_structure Cytokine 030220 oncology & carcinogenesis Cancer research Medicine Female Stromal Cells Stem cell Research Article |
| Zdroj: | JCI Insight JCI Insight, Vol 5, Iss 22 (2020) |
| ISSN: | 2379-3708 |
| Popis: | 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. Bone marrow Tregs regulate stromal cell function to maintain hematopoiesis through IL-10 and provide a potential therapeutic avenue for stromal manipulation. |
| Databáze: | OpenAIRE |
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