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CD11c(+) cells control platelet homeostasis in a murine bone marrow chimeric atherosclerosis model

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Item Type:Article
Title:CD11c(+) cells control platelet homeostasis in a murine bone marrow chimeric atherosclerosis model
Creators Name:Sauter, Manuela, Gregori, Serena, Langer, Harald F. and Sauter, Reinhard J.
Abstract:BACKGROUND/OBJECTIVES: Dendritic cells (DCs) are key regulators of immune responses in cardiovascular disease, yet their role in platelet homeostasis and thrombopoiesis remains incompletely understood. We previously demonstrated that chronic depletion of CD11c(+) cells accelerates atherosclerotic plaque development. The objective of this study was to determine whether sustained loss of CD11c(+) cells alters platelet production and systemic inflammatory signaling under atherogenic conditions. METHODS: CD11c-DTR bone marrow chimeric mice on ApoE(-/-) background were generated and fed a high-cholesterol diet. CD11c(+) cells were depleted by repeated diphtheria toxin administration over six weeks. Circulating platelet counts were quantified by automated hematology analysis. Systemic inflammatory changes were assessed using serum cytokine and chemokine profiling, and serum thrombopoietin (TPO) levels were measured by ELISA. RESULTS: Chronic CD11c(+) cell depletion resulted in a significant increase in circulating platelet counts in ApoE(-/-) mice. Serum cytokine profiling revealed broad inflammatory remodeling, including increased levels of cytokines associated with megakaryopoiesis and platelet activation, such as IL-4, MCP-1, CXCL9, IL-16, and IL-1α. In parallel, serum TPO levels were significantly elevated following CD11c(+) cell depletion. CONCLUSIONS: In the specific context of hyperlipidemic CD11c-DTR bone marrow chimeric mice, these findings demonstrate that loss of CD11c(+) cells is associated with a pro-thrombopoietic shift, elevated platelet counts, and systemic inflammatory changes. Our data identify a CD11c(+) cell-TPO-platelet axis linking immune regulation to platelet homeostasis and thrombo-inflammatory signaling under these specific atherogenic conditions.
Keywords:CD11c(+) Dendritic Cells, Thrombopoiesis, Platelets, Atherosclerosis, Thrombopoietin, Inflammation, Animals, Mice
Source:Biomedicines
ISSN:2227-9059
Publisher:MDPI
Volume:14
Number:2
Page Range:342
Date:2 February 2026
Official Publication:https://doi.org/10.3390/biomedicines14020342
PubMed:View item in PubMed

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