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Myeloid cells promote interferon signaling-associated deterioration of the hematopoietic system.

ABSTRACT: Innate and adaptive immune cells participate in the homeostatic regulation of hematopoietic stem cells (HSCs). Here, we interrogate the contribution of myeloid cells, the most abundant cell type in the mammalian bone marrow, in a clinically relevant mouse model of neutropenia. Long-term genetic depletion of neutrophils and eosinophils results in activation of multipotent progenitors but preservation of HSCs. Depletion of myeloid cells abrogates HSC expansion, loss of serial repopulation and lymphoid reconstitution capacity and remodeling of HSC niches, features previously associated with hematopoietic aging. This is associated with mitigation of interferon signaling in both HSCs and their niches via reduction of NK cell number and activation. These data implicate myeloid cells in the functional decline of hematopoiesis, associated with activation of interferon signaling via a putative neutrophil-NK cell axis. Innate immunity may thus come at the cost of system deterioration through enhanced chronic inflammatory signaling to stem cells and their niches.

SUBMITTER: Feyen J

PROVIDER: S-EPMC9741615 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Myeloid cells promote interferon signaling-associated deterioration of the hematopoietic system.

Feyen Jacqueline J Ping Zhen Z Chen Lanpeng L van Dijk Claire C van Tienhoven Tim V D TVD van Strien Paulina M H PMH Hoogenboezem Remco M RM Wevers Michiel J W MJW Sanders Mathijs A MA Touw Ivo P IP Raaijmakers Marc H G P MHGP

Nature communications 20221210 1

Innate and adaptive immune cells participate in the homeostatic regulation of hematopoietic stem cells (HSCs). Here, we interrogate the contribution of myeloid cells, the most abundant cell type in the mammalian bone marrow, in a clinically relevant mouse model of neutropenia. Long-term genetic depletion of neutrophils and eosinophils results in activation of multipotent progenitors but preservation of HSCs. Depletion of myeloid cells abrogates HSC expansion, loss of serial repopulation and lymp ...[more]

PMID: 36496394

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Myeloid cells promote interferon signaling-associated deterioration of the hematopoietic system.

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Myeloid cells promote interferon signaling-associated deterioration of the hematopoietic system.

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