Host factor TIMP1 sustains long-lasting myeloid-biased hematopoiesis after severe infection.
Journal
The Journal of experimental medicine
ISSN: 1540-9538
Titre abrégé: J Exp Med
Pays: United States
ID NLM: 2985109R
Informations de publication
Date de publication:
04 12 2023
04 12 2023
Historique:
received:
03
01
2023
revised:
10
07
2023
accepted:
03
10
2023
pmc-release:
18
04
2024
medline:
23
10
2023
pubmed:
18
10
2023
entrez:
18
10
2023
Statut:
ppublish
Résumé
Infection is able to promote innate immunity by enhancing a long-term myeloid output even after the inciting infectious agent has been cleared. However, the mechanisms underlying such a regulation are not fully understood. Using a mouse polymicrobial peritonitis (sepsis) model, we show that severe infection leads to increased, sustained myelopoiesis after the infection is resolved. In post-infection mice, the tissue inhibitor of metalloproteinases 1 (TIMP1) is constitutively upregulated. TIMP1 antagonizes the function of ADAM10, an essential cleavage enzyme for the activation of the Notch signaling pathway, which suppresses myelopoiesis. While TIMP1 is dispensable for myelopoiesis under the steady state, increased TIMP1 enhances myelopoiesis after infection. Thus, our data establish TIMP1 as a molecular reporter of past infection in the host, sustaining hyper myelopoiesis and serving as a potential therapeutic target for modulating HSPC cell fate.
Identifiants
pubmed: 37851372
pii: 276338
doi: 10.1084/jem.20230018
pmc: PMC10585121
pii:
doi:
Substances chimiques
Tissue Inhibitor of Metalloproteinase-1
0
Timp1 protein, mouse
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIAID NIH HHS
ID : P01 AI102852
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL152099
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI059742
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL144436
Pays : United States
Informations de copyright
© 2023 Song et al.
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