RT info:eu-repo/semantics/article
T1 NAD+ regulates Treg cell fate and promotes allograft survival via a systemic IL-10 production that is CD4+ CD25+ Foxp3+ T cells independent
A1 Elkhal, Abdallah
A1 Rodriguez-Cetina Biefer, Héctor
A1 Heinbokel, Timm
A1 Uehara, Hirofumi
A1 Quante, Markus
A1 Seyda, Midas
A1 Schuitenmaker, Jeroen M.
A1 Krenzien, Felix
A1 Camacho, Virginia
A1 Fuente García, Miguel Ángel de la
A1 Ghiran, Ionita
A1 Tullius, Stefan G.
K1 T cells
K1 Células T
K1 Nicotinamide adenine dinucleotide
K1 Nicotinamida adenina dinucleótido
AB CD4+ CD25+ Foxp3+ Tregs have been shown to play a central role in immune homeostasis whilepreventing from fatal inflammatory responses, while Th17 cells have traditionally been recognizedas pro-inflammatory mediators implicated in a myriad of diseases. Studies have shown the potentialof Tregs to convert into Th17 cells, and Th17 cells into Tregs. Increasing evidence have pointed outCD25 as a key molecule during this transdifferentiation process, however molecules that allow suchdevelopment remain unknown. Here, we investigated the impact of NAD+ on the fate of CD4+ CD25+Foxp3+ Tregs in-depth, dissected their transcriptional signature profile and explored mechanismsunderlying their conversion into IL-17A producing cells. Our results demonstrate that NAD+ promotesTreg conversion into Th17 cells in vitro and in vivo via CD25 cell surface marker. Despite the reducednumber of Tregs, known to promote homeostasis, and an increased number of pro-inflammatoryTh17 cells, NAD+ was able to promote an impressive allograft survival through a robust systemicIL-10 production that was CD4+ CD25+ Foxp3+ independent. Collectively, our study unravels a novelimmunoregulatory mechanism of NAD+ that regulates Tregs fate while promoting allograft survivalthat may have clinical applications in alloimmunity and in a wide spectrum of inflammatory conditions.
PB Springer Nature
SN 2045-2322
YR 2016
FD 2016
LK http://uvadoc.uva.es/handle/10324/44633
UL http://uvadoc.uva.es/handle/10324/44633
LA eng
NO Scientific Reports, 2016, vol. 6. 12 p.
NO Producción Científica
DS UVaDOC
RD 22-dic-2024