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

Jacqueline Feyen, Zhen Ping, Lanpeng Chen, Claire van Dijk, Tim V.D. van Tienhoven, Paulina M.H. van Strien, Remco M. Hoogenboezem, Michiel J.W. Wevers, Mathijs A. Sanders, Ivo P. Touw, Marc H.G.P. Raaijmakers*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)
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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.

Original languageEnglish
Article number7657
JournalNature Communications
Volume13
Issue number1
DOIs
Publication statusPublished - 10 Dec 2022

Bibliographical note

Acknowledgements:
We thank Michael Vermeulen, Natalie Papazian, Dr. Eric Bindels, Dr. Kirsten van Lom, Dr. Elwin Rombouts, Dr. Giulia Corradi, Dr. Tamar Tak, Eline Pronk, Paola Pisterzi and Martijn Ernst for technical assistance; members of the Erasmus MC animal core facility EDC for their help with animal care. This work was supported by grants from the Shwachman–Diamond Syndrome Foundation and the Dutch Cancer Society (EMCR 2017-11092) to M.H.G.P.R.

Publisher Copyright: © 2022, The Author(s).

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