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Critical role of OX40 in the expansion and survival of CD4 T-cell-derived double-negative T cells

CD4(+) T-cell-converted CD4(−)CD8(−) double negative (cDNT) have strong suppressive activity in the maintenance of immune tolerance, whereas IL-2 promotes cDNT proliferation and enhances cDNT resistance to apoptosis. However, the intrinsic mechanisms that regulate the survival of cDNT are still unkn...

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Autores principales: Sun, Guangyong, Sun, Xiaojing, Li, Wei, Liu, Kai, Tian, Dan, Dong, Yiran, Sun, Xuelian, Xu, Hufeng, Zhang, Dong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5966453/
https://www.ncbi.nlm.nih.gov/pubmed/29795285
http://dx.doi.org/10.1038/s41419-018-0659-x
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author Sun, Guangyong
Sun, Xiaojing
Li, Wei
Liu, Kai
Tian, Dan
Dong, Yiran
Sun, Xuelian
Xu, Hufeng
Zhang, Dong
author_facet Sun, Guangyong
Sun, Xiaojing
Li, Wei
Liu, Kai
Tian, Dan
Dong, Yiran
Sun, Xuelian
Xu, Hufeng
Zhang, Dong
author_sort Sun, Guangyong
collection PubMed
description CD4(+) T-cell-converted CD4(−)CD8(−) double negative (cDNT) have strong suppressive activity in the maintenance of immune tolerance, whereas IL-2 promotes cDNT proliferation and enhances cDNT resistance to apoptosis. However, the intrinsic mechanisms that regulate the survival of cDNT are still unknown. Here we demonstrate that the OX40 molecule was highly expressed on cDNT. The expression of OX40 was necessary to promote proliferation and inhibit apoptosis of cDNT in vivo and in vitro. OX40 promoted the survival of cDNT by regulating the expression of Bcl-2, Bcl-xL, Survivin, and BCL2L11. Canonical NF-κB cell signaling played an important role in the transmission of essential division and survival signals through OX40 in cDNT. IL-2 promoted the survival of cDNT in part via elevating the expression of the OX40 molecule. IL-2 promoted OX40 expression via downregulating the PPARα expression. In conclusion, we elucidated that OX40 is a key molecule that regulates cDNT proliferation and survival. IL-2 promoted OX40 expression by downregulating the PPARα binding to the OX40 promoter, leading to the elevated expression of Bcl-2, Bcl-xL, and Survivin in cDNT, which finally resulted in the promoted proliferation and decreased apoptosis of cDNT.
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spelling pubmed-59664532018-05-24 Critical role of OX40 in the expansion and survival of CD4 T-cell-derived double-negative T cells Sun, Guangyong Sun, Xiaojing Li, Wei Liu, Kai Tian, Dan Dong, Yiran Sun, Xuelian Xu, Hufeng Zhang, Dong Cell Death Dis Article CD4(+) T-cell-converted CD4(−)CD8(−) double negative (cDNT) have strong suppressive activity in the maintenance of immune tolerance, whereas IL-2 promotes cDNT proliferation and enhances cDNT resistance to apoptosis. However, the intrinsic mechanisms that regulate the survival of cDNT are still unknown. Here we demonstrate that the OX40 molecule was highly expressed on cDNT. The expression of OX40 was necessary to promote proliferation and inhibit apoptosis of cDNT in vivo and in vitro. OX40 promoted the survival of cDNT by regulating the expression of Bcl-2, Bcl-xL, Survivin, and BCL2L11. Canonical NF-κB cell signaling played an important role in the transmission of essential division and survival signals through OX40 in cDNT. IL-2 promoted the survival of cDNT in part via elevating the expression of the OX40 molecule. IL-2 promoted OX40 expression via downregulating the PPARα expression. In conclusion, we elucidated that OX40 is a key molecule that regulates cDNT proliferation and survival. IL-2 promoted OX40 expression by downregulating the PPARα binding to the OX40 promoter, leading to the elevated expression of Bcl-2, Bcl-xL, and Survivin in cDNT, which finally resulted in the promoted proliferation and decreased apoptosis of cDNT. Nature Publishing Group UK 2018-05-23 /pmc/articles/PMC5966453/ /pubmed/29795285 http://dx.doi.org/10.1038/s41419-018-0659-x Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Sun, Guangyong
Sun, Xiaojing
Li, Wei
Liu, Kai
Tian, Dan
Dong, Yiran
Sun, Xuelian
Xu, Hufeng
Zhang, Dong
Critical role of OX40 in the expansion and survival of CD4 T-cell-derived double-negative T cells
title Critical role of OX40 in the expansion and survival of CD4 T-cell-derived double-negative T cells
title_full Critical role of OX40 in the expansion and survival of CD4 T-cell-derived double-negative T cells
title_fullStr Critical role of OX40 in the expansion and survival of CD4 T-cell-derived double-negative T cells
title_full_unstemmed Critical role of OX40 in the expansion and survival of CD4 T-cell-derived double-negative T cells
title_short Critical role of OX40 in the expansion and survival of CD4 T-cell-derived double-negative T cells
title_sort critical role of ox40 in the expansion and survival of cd4 t-cell-derived double-negative t cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5966453/
https://www.ncbi.nlm.nih.gov/pubmed/29795285
http://dx.doi.org/10.1038/s41419-018-0659-x
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