2024-03-29T07:44:53Zhttps://uvadoc.uva.es/oai/requestoai:uvadoc.uva.es:10324/446332021-06-24T07:17:55Zcom_10324_43677com_10324_954com_10324_894col_10324_43678
NAD+ regulates Treg cell fate and promotes allograft survival via a systemic IL-10 production that is CD4+ CD25+ Foxp3+ T cells independent
Elkhal, Abdallah
Rodriguez-Cetina Biefer, Héctor
Heinbokel, Timm
Uehara, Hirofumi
Quante, Markus
Seyda, Midas
Schuitenmaker, Jeroen M.
Krenzien, Felix
Camacho, Virginia
Fuente García, Miguel Ángel de la
Ghiran, Ionita
Tullius, Stefan G.
T cells
Células T
Nicotinamide adenine dinucleotide
Nicotinamida adenina dinucleótido
Producción Científica
CD4+ CD25+ Foxp3+ Tregs have been shown to play a central role in immune homeostasis while
preventing from fatal inflammatory responses, while Th17 cells have traditionally been recognized
as pro-inflammatory mediators implicated in a myriad of diseases. Studies have shown the potential
of Tregs to convert into Th17 cells, and Th17 cells into Tregs. Increasing evidence have pointed out
CD25 as a key molecule during this transdifferentiation process, however molecules that allow such
development 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 mechanisms
underlying their conversion into IL-17A producing cells. Our results demonstrate that NAD+ promotes
Treg conversion into Th17 cells in vitro and in vivo via CD25 cell surface marker. Despite the reduced
number of Tregs, known to promote homeostasis, and an increased number of pro-inflammatory
Th17 cells, NAD+ was able to promote an impressive allograft survival through a robust systemic
IL-10 production that was CD4+ CD25+ Foxp3+ independent. Collectively, our study unravels a novel
immunoregulatory mechanism of NAD+ that regulates Tregs fate while promoting allograft survival
that may have clinical applications in alloimmunity and in a wide spectrum of inflammatory conditions.
National Institutes of Health (grants R01AG039449 and R01HL096795)
German Research Foundation (grant KFO243/1)
Instituto de Salud Carlos III (grant PI10/02 511)
Fundación Ramón Areces (grant CIVP16A1843)
2021-01-07T11:30:18Z
2021-01-07T11:30:18Z
2016
info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
Scientific Reports, 2016, vol. 6. 12 p.
2045-2322
http://uvadoc.uva.es/handle/10324/44633
10.1038/srep22325
eng
https://www.nature.com/articles/srep22325
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
© 2016 Springer Nature
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Hispana
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http://creativecommons.org/licenses/by-nc-nd/4.0/
UVaDOC. Repositorio Documental de la Universidad de Valladolid
http://uvadoc.uva.es/handle/10324/44633