TY - JOUR
T1 - HIF1α-dependent metabolic reprogramming governs mesenchymal stem/stromal cell immunoregulatory functions
AU - Contreras-Lopez, Rafael
AU - Elizondo-Vega, Roberto
AU - Paredes, Maria Jose
AU - Luque-Campos, Noymar
AU - Torres, Maria Jose
AU - Tejedor, Gautier
AU - Vega-Letter, Ana Maria
AU - Figueroa-Valdés, Aliosha
AU - Pradenas, Carolina
AU - Oyarce, Karina
AU - Jorgensen, Christian
AU - Khoury, Maroun
AU - Garcia-Robles, Maria de los Angeles
AU - Altamirano, Claudia
AU - Djouad, Farida
AU - Luz-Crawford, Patricia
PY - 2020/6/1
Y1 - 2020/6/1
N2 - 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.
AB - 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.
KW - glycolytic
KW - HIF1α
KW - immunomodulation
KW - immunosuppression
KW - metabolic reprogramming
KW - metabolism
KW - MSCs
KW - glycolytic
KW - HIF1α
KW - immunomodulation
KW - immunosuppression
KW - metabolic reprogramming
KW - metabolism
KW - MSCs
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85084070345&origin=inward
UR - https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85084070345&origin=inward
U2 - 10.1096/fj.201902232R
DO - 10.1096/fj.201902232R
M3 - Article
VL - 34
SP - 8250
EP - 8264
JO - FASEB Journal
JF - FASEB Journal
SN - 0892-6638
IS - 6
ER -