IL-1β expression in bone marrow dendritic cells is induced by TLR2 agonists and regulates HSC function.

Autor:	Li S; Division of Oncology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO.; Hematology Oncology Center, Beijing Children's Hospital, National Center for Children's Health, Capital Medial University, Beijing, China.; Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China., Yao JC; Division of Oncology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO., Oetjen KA; Division of Oncology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO., Krambs JR; Division of Oncology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO., Xia J; Division of Oncology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO., Zhang J; Division of Oncology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO., Schmidt AP; Division of Oncology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO., Helton NM; Division of Oncology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO., Fulton RS; McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO., Heath SE; Division of Oncology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO., Turnbull IR; Department of Surgery, Washington University School of Medicine, St. Louis, MO., Mbalaviele G; Division of Bone and Mineral Disease, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO., Ley TJ; Division of Oncology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO., Walter MJ; Division of Oncology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO., Link DC; Division of Oncology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO.
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2022 Oct 06; Vol. 140 (14), pp. 1607-1620.
DOI:	10.1182/blood.2022016084
Abstrakt:	Hematopoietic stem/progenitor cells (HSPCs) reside in localized microenvironments, or niches, in the bone marrow that provide key signals regulating their activity. A fundamental property of hematopoiesis is the ability to respond to environmental cues such as inflammation. How these cues are transmitted to HSPCs within hematopoietic niches is not well established. Here, we show that perivascular bone marrow dendritic cells (DCs) express a high basal level of Toll-like receptor-1 (TLR1) and TLR2. Systemic treatment with a TLR1/2 agonist induces HSPC expansion and mobilization. It also induces marked alterations in the bone marrow microenvironment, including a decrease in osteoblast activity and sinusoidal endothelial cell numbers. TLR1/2 agonist treatment of mice in which Myd88 is deleted specifically in DCs using Zbtb46-Cre show that the TLR1/2-induced expansion of multipotent HPSCs, but not HSPC mobilization or alterations in the bone marrow microenvironment, is dependent on TLR1/2 signaling in DCs. Interleukin-1β (IL-1β) is constitutively expressed in both murine and human DCs and is further induced after TLR1/2 stimulation. Systemic TLR1/2 agonist treatment of Il1r1-/- mice show that TLR1/2-induced HSPC expansion is dependent on IL-1β signaling. Single-cell RNA-sequencing of low-risk myelodysplastic syndrome bone marrow revealed that IL1B and TLR1 expression is increased in DCs. Collectively, these data suggest a model in which TLR1/2 stimulation of DCs induces secretion of IL-1β and other inflammatory cytokines into the perivascular niche, which in turn, regulates multipotent HSPCs. Increased DC TLR1/2 signaling may contribute to altered HSPC function in myelodysplastic syndrome by increasing local IL-1β expression. (© 2022 by The American Society of Hematology.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu