HIF1α-dependent metabolic reprogramming governs mesenchymal stem/stromal cell immunoregulatory functions

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dc.coverageDOI: 10.1096/fj.201902232R
dc.creatorContreras-Lopez, Rafael
dc.creatorElizondo-Vega, Roberto
dc.creatorParedes, Maria Jose
dc.creatorLuque-Campos, Noymar
dc.creatorTorres, Maria Jose
dc.creatorTejedor, Gautier
dc.creatorVega-Letter, Ana Maria
dc.creatorFigueroa-Valdés, Aliosha
dc.creatorPradenas, Carolina
dc.creatorOyarce, Karina
dc.creatorJorgensen, Christian
dc.creatorKhoury, Maroun
dc.creatorGarcia-Robles, Maria de los Angeles
dc.creatorAltamirano, Claudia
dc.creatorDjouad, Farida
dc.creatorLuz Crawford, Patricia Alejandra
dc.date2020
dc.date.accessioned2025-11-18T19:47:39Z
dc.date.available2025-11-18T19:47:39Z
dc.description<p>Hypoxia-inducible factor 1 α (HIF1α), a regulator of metabolic change, is required for the survival and differentiation potential of mesenchymal stem/stromal cells (MSC). Its role in MSC immunoregulatory activity, however, has not been completely elucidated. In the present study, we evaluate the role of HIF1α on MSC immunosuppressive potential. We show that HIF1α silencing in MSC decreases their inhibitory potential on Th1 and Th17 cell generation and limits their capacity to generate regulatory T cells. This reduced immunosuppressive potential of MSC is associated with a metabolic switch from glycolysis to OXPHOS and a reduced capacity to express or produce some immunosuppressive mediators including Intercellular Adhesion Molecule (ICAM), IL-6, and nitric oxide (NO). Moreover, using the Delayed-Type Hypersensitivity murine model (DTH), we confirm, in vivo, the critical role of HIF1α on MSC immunosuppressive effect. Indeed, we show that HIF1α silencing impairs MSC capacity to reduce inflammation and inhibit the generation of pro-inflammatory T cells. This study reveals the pivotal role of HIF1α on MSC immunosuppressive activity through the regulation of their metabolic status and identifies HIF1α as a novel mediator of MSC immunotherapeutic potential.</p>eng
dc.descriptionHypoxia-inducible factor 1 α (HIF1α), a regulator of metabolic change, is required for the survival and differentiation potential of mesenchymal stem/stromal cells (MSC). Its role in MSC immunoregulatory activity, however, has not been completely elucidated. In the present study, we evaluate the role of HIF1α on MSC immunosuppressive potential. We show that HIF1α silencing in MSC decreases their inhibitory potential on Th1 and Th17 cell generation and limits their capacity to generate regulatory T cells. This reduced immunosuppressive potential of MSC is associated with a metabolic switch from glycolysis to OXPHOS and a reduced capacity to express or produce some immunosuppressive mediators including Intercellular Adhesion Molecule (ICAM), IL-6, and nitric oxide (NO). Moreover, using the Delayed-Type Hypersensitivity murine model (DTH), we confirm, in vivo, the critical role of HIF1α on MSC immunosuppressive effect. Indeed, we show that HIF1α silencing impairs MSC capacity to reduce inflammation and inhibit the generation of pro-inflammatory T cells. This study reveals the pivotal role of HIF1α on MSC immunosuppressive activity through the regulation of their metabolic status and identifies HIF1α as a novel mediator of MSC immunotherapeutic potential.spa
dc.identifierhttps://investigadores.uandes.cl/en/publications/f8c39d1a-c7bb-4127-9bbc-9192b9607600
dc.identifier.urihttps://repositorio.uandes.cl/handle/uandes/55148
dc.languageeng
dc.rightsinfo:eu-repo/semantics/openAccess
dc.sourcevol.34 (2020) date: 2020-06-01 nr.6 p.8250-8264
dc.subjectHIF1α
dc.subjectMSCs
dc.subjectglycolytic
dc.subjectimmunomodulation
dc.subjectimmunosuppression
dc.subjectmetabolic reprogramming
dc.subjectmetabolism
dc.titleHIF1α-dependent metabolic reprogramming governs mesenchymal stem/stromal cell immunoregulatory functionseng
dc.typeArticleeng
dc.typeArtículospa
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