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

Autor: Feyen J; Department of Hematology, Erasmus MC Cancer Institute, 3015CN, Rotterdam, the Netherlands., Ping Z; Department of Hematology, Erasmus MC Cancer Institute, 3015CN, Rotterdam, the Netherlands., Chen L; Department of Hematology, Erasmus MC Cancer Institute, 3015CN, Rotterdam, the Netherlands., van Dijk C; Department of Hematology, Erasmus MC Cancer Institute, 3015CN, Rotterdam, the Netherlands., van Tienhoven TVD; Department of Hematology, Erasmus MC Cancer Institute, 3015CN, Rotterdam, the Netherlands., van Strien PMH; Department of Hematology, Erasmus MC Cancer Institute, 3015CN, Rotterdam, the Netherlands., Hoogenboezem RM; Department of Hematology, Erasmus MC Cancer Institute, 3015CN, Rotterdam, the Netherlands., Wevers MJW; Department of Hematology, Erasmus MC Cancer Institute, 3015CN, Rotterdam, the Netherlands., Sanders MA; Department of Hematology, Erasmus MC Cancer Institute, 3015CN, Rotterdam, the Netherlands., Touw IP; Department of Hematology, Erasmus MC Cancer Institute, 3015CN, Rotterdam, the Netherlands., Raaijmakers MHGP; Department of Hematology, Erasmus MC Cancer Institute, 3015CN, Rotterdam, the Netherlands. m.h.g.raaijmakers@erasmusmc.nl.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Dec 10; Vol. 13 (1), pp. 7657. Date of Electronic Publication: 2022 Dec 10.
DOI: 10.1038/s41467-022-35318-x
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
Externí odkaz: