Journal article
GM-CSF drives dysregulated hematopoietic stem cell activity and pathogenic extramedullary myelopoiesis in experimental spondyloarthritis
- Abstract:
- Dysregulated hematopoiesis occurs in several chronic inflammatory diseases, but it remains unclear how hematopoietic stem cells (HSCs) in the bone marrow (BM) sense peripheral inflammation and contribute to tissue damage. Here, we show the HSC gene expression program is biased toward myelopoiesis and differentiation skewed toward granulocyte-monocyte progenitors (GMP) during joint and intestinal inflammation in experimental spondyloarthritis (SpA). GM-CSF-receptor is increased on HSC and multipotent progenitors, favoring a striking increase in myelopoiesis at the earliest hematopoietic stages. GMP accumulate in the BM in SpA and, unexpectedly, at extramedulary sites: in the inflamed joints and spleen. Furthermore we show that GM-CSF promotes BM and extramedullary myelopoiesis, tissue-toxic neutrophil accumulation in target organs, and GM-CSF prophylactic or therapeutic blockade substantially decreases SpA severity. Surprisingly, besides CD4 T cells and innate lymphoid cells, mast cells (MC) are a source of GM-CSF in inflammation, and its pathogenic production is promoted by the alarmin IL-33.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 3.0MB, Terms of use)
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- Publisher copy:
- 10.1038/s41467-019-13853-4
Authors
- Publisher:
- Nature Research
- Journal:
- Nature Communications More from this journal
- Volume:
- 11
- Issue:
- 2020
- Article number:
- 155
- Publication date:
- 2020-01-09
- Acceptance date:
- 2019-12-02
- DOI:
- ISSN:
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2041-1723
- Pubs id:
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pubs:1081263
- UUID:
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uuid:d3dd80bb-30db-44f2-842b-6f7abc151f02
- Local pid:
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pubs:1081263
- Source identifiers:
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1081263
- Deposit date:
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2020-01-08
Terms of use
- Copyright holder:
- Regan-Komito et al
- Copyright date:
- 2020
- Notes:
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© The Author(s) 2020. This article is licensed under a Creative Commons
Attribution 4.0 International License, which permits use, sharing,
adaptation, distribution and reproduction in any medium or format, as long as you give
appropriate credit to the original author(s) and the source, provide a link to the Creative
Commons license, and indicate if changes were made. The images or other third party
material in this article are included in the article’s Creative Commons license, unless
indicated otherwise in a credit line to the material. If material is not included in the
article’s Creative Commons license and your intended use is not permitted by statutory
regulation or exceeds the permitted use, you will need to obtain permission directly from
the copyright holder. To view a copy of this license, visit http://creativecommons.org/
licenses/by/4.0/.
- Licence:
- CC Attribution (CC BY)
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