Type I interferon signaling controls the early hematopoietic expansion in response to β-glucan

Summary: Rapid hematopoietic adaptations are important for building and sustaining the biological response to β-glucan. The signals involved in these early events have not yet been fully explored. Given that type I interferons are produced in response to β-glucan and can profoundly impact hematopoie...

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Main Authors: Yangsong Xu, Man K.S. Lee, Nicole A. de Weerd, Ziyue Fu, Camilla Bertuzzo Veiga, Dragana Dragoljevic, Dmitri Sviridov, Paul J. Hertzog, Andrew J. Fleetwood, Andrew J. Murphy
Format: Article
Language:English
Published: Elsevier 2025-05-01
Series:iScience
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Online Access:http://www.sciencedirect.com/science/article/pii/S258900422500608X
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Summary:Summary: Rapid hematopoietic adaptations are important for building and sustaining the biological response to β-glucan. The signals involved in these early events have not yet been fully explored. Given that type I interferons are produced in response to β-glucan and can profoundly impact hematopoietic stem cell (HSC) function, we hypothesized that this pathway may be involved in the early bone marrow response to β-glucan. In vivo administration of β-glucan led to local interferon-α production in the peritoneal cavity and bone marrow, upregulation of its receptor, IFNAR1, specifically on long-term hematopoietic stem cells (LT-HSCs), and broad expansion of downstream progenitor subpopulations. We demonstrate that intact type I interferon signaling is critical for β-glucan-mediated LT-HSC proliferation, mitochondrial activity, and glycolytic commitment. By determining that type I interferon signaling is important for LT-HSCs, which sit at the apex of the hematopoietic hierarchy, we uncover an important component of the early inflammatory response to β-glucan.
ISSN:2589-0042