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

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New publication by Alberich-Jorda M and Sladana Kosanovic in EMBO reports.

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.

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16 November 2022/by KOM Agency
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https://www.enhpathy.eu/wp-content/uploads/2022/11/Publication-EMBO-reports-final.jpg 680 680 KOM Agency https://www.enhpathy.eu/wp-content/uploads/2019/11/logo-enhpathy-1.png KOM Agency2022-11-16 16:27:322022-11-16 16:36:02Chronic inflammation decreases HSC fitness by activating the druggable Jak/Stat3 signaling pathway

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Marie CurieThis project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 860002. The information contained in this website reflects only the authors’ view. REA and EC are not responsible for any use that may be made of this information.

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ENHPATHY ESRs visit the Novartis Institutes for BioMedical Research (NIBR) Current challenges in understanding the role of enhancers in disease
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