Interleukin-1 contributes to clonal expansion and progression of bone marrow fibrosis in JAK2V617F-induced myeloproliferative neoplasm.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
13 09 2022
13 09 2022
Historique:
received:
09
07
2021
accepted:
24
08
2022
entrez:
13
9
2022
pubmed:
14
9
2022
medline:
16
9
2022
Statut:
epublish
Résumé
Chronic inflammation is frequently associated with myeloproliferative neoplasms (MPN), but the role of inflammation in the pathogenesis of MPN remains unclear. Expression of the proinflammatory cytokine interleukin-1 (IL-1) is elevated in patients with MPN as well as in Jak2V617F knock-in mice. Here, we show that genetic deletion of IL-1 receptor 1 (IL-1R1) normalizes peripheral blood counts, reduces splenomegaly and ameliorates bone marrow fibrosis in homozygous Jak2V617F mouse model of myelofibrosis. Deletion of IL-1R1 also significantly reduces Jak2V617F mutant hematopoietic stem/progenitor cells. Exogenous administration of IL-1β enhances myeloid cell expansion and accelerates the development of bone marrow fibrosis in heterozygous Jak2V617F mice. Furthermore, treatment with anti-IL-1R1 antibodies significantly reduces leukocytosis and splenomegaly, and ameliorates bone marrow fibrosis in homozygous Jak2V617F mice. Collectively, these results suggest that IL-1 signaling plays a pathogenic role in MPN disease progression, and targeting of IL-1R1 could be a useful strategy for the treatment of myelofibrosis.
Identifiants
pubmed: 36100596
doi: 10.1038/s41467-022-32928-3
pii: 10.1038/s41467-022-32928-3
pmc: PMC9470702
doi:
Substances chimiques
IL1R1 protein, mouse
0
Interleukin-1
0
Receptors, Interleukin-1 Type I
0
Jak2 protein, mouse
EC 2.7.10.2
Janus Kinase 2
EC 2.7.10.2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
5347Subventions
Organisme : NCI NIH HHS
ID : P30 CA044579
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL095685
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL149893
Pays : United States
Informations de copyright
© 2022. The Author(s).
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