Chronic inflammation decreases HSC fitness by activating the druggable Jak/Stat3 signaling pathway

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F23%3A00566133" target="_blank" >RIV/68378050:_____/23:00566133 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11130/23:10449818 RIV/00216208:11310/23:10449818
Result on the web
<a href="https://www.embopress.org/doi/full/10.15252/embr.202254729" target="_blank" >https://www.embopress.org/doi/full/10.15252/embr.202254729</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.15252/embr.202254729" target="_blank" >10.15252/embr.202254729</a>

Result language
angličtina
Original language name
Chronic inflammation decreases HSC fitness by activating the druggable Jak/Stat3 signaling pathway
Original language description
Chronic inflammation represents a major threat to human health since long-term systemic inflammation is known to affect distinct tissues and organs. Recently, solid evidence demonstrated that chronic inflammation affects hematopoiesis, however, how chronic inflammation affects hematopoietic stem cells (HSCs) on the mechanistic level is poorly understood. Here, we employ a mouse model of chronic multifocal osteomyelitis (CMO) to assess the effects of a spontaneously developed inflammatory condition on HSCs. We demonstrate that hematopoietic and nonhematopoietic compartments in CMO BM contribute to HSC expansion and impair their function. Remarkably, our results suggest that the typical features of murine multifocal osteomyelitis and the HSC phenotype are mechanistically decoupled. We show that the CMO environment imprints a myeloid gene signature and imposes a pro-inflammatory profile on HSCs. We identify IL-6 and the Jak/Stat3 signaling pathway as critical mediators. However, while IL-6 and Stat3 blockage reduce HSC numbers in CMO mice, only inhibition of Stat3 activity significantly rescues their fitness. Our data emphasize the detrimental effects of chronic inflammation on stem cell function, opening new venues for treatment.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology

Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2023
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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