NKG2D+CD4+ T Cells Kill Regulatory T Cells in a NKG2D-NKG2D Ligand- Dependent Manner in Systemic Lupus Erythematosus

Abstract Systemic lupus erythematosus (SLE) features a decreased pool of CD4+CD25+Foxp3+ T regulatory (Treg) cells. We had previously observed NKG2D+CD4+ T cell expansion in contrast to a decreased pool of Treg cells in SLE patients, but whether NKG2D+CD4+ T cells contribute to the decreased Treg ce...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Di Yang, Zhiqiang Tian, Mengjie Zhang, Weibing Yang, Jun Tang, Yuzhang Wu, Bing Ni
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2514c9158e8249eca56a54d544dcbea3
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:2514c9158e8249eca56a54d544dcbea3
record_format	dspace
spelling	oai:doaj.org-article:2514c9158e8249eca56a54d544dcbea32021-12-02T15:05:49ZNKG2D+CD4+ T Cells Kill Regulatory T Cells in a NKG2D-NKG2D Ligand- Dependent Manner in Systemic Lupus Erythematosus10.1038/s41598-017-01379-y2045-2322https://doaj.org/article/2514c9158e8249eca56a54d544dcbea32017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01379-yhttps://doaj.org/toc/2045-2322Abstract Systemic lupus erythematosus (SLE) features a decreased pool of CD4+CD25+Foxp3+ T regulatory (Treg) cells. We had previously observed NKG2D+CD4+ T cell expansion in contrast to a decreased pool of Treg cells in SLE patients, but whether NKG2D+CD4+ T cells contribute to the decreased Treg cells remains unclear. In the present study, we found that the NKG2D+CD4+ T cells efficiently killed NKG2D ligand (NKG2DL)+ Treg cells in vitro, whereby the surviving Treg cells in SLE patients showed no detectable expression of NKG2DLs. It was further found that MRL/lpr lupus mice have significantly increased percentage of NKG2D+CD4+ T cells and obvious decreased percentage of Treg cells, as compared with wild-type mice. Adoptively transferred NKG2DL+ Treg cells were found to be efficiently killed in MRL/lpr lupus mice, with NKG2D neutralization remarkably attenuating this killing. Anti-NKG2D or anti-interferon-alpha receptor (IFNAR) antibodies treatment in MRL/lpr mice restored Treg cells numbers and markedly ameliorated the lupus disease. These results suggest that NKG2D+CD4+ T cells are involved in the pathogenesis of SLE by killing Treg cells in a NKG2D-NKG2DL-dependent manner. Targeting the NKG2D-NKG2DL interaction might be a potential therapeutic strategy by which Treg cells can be protected from cytolysis in SLE patients.Di YangZhiqiang TianMengjie ZhangWeibing YangJun TangYuzhang WuBing NiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Di Yang Zhiqiang Tian Mengjie Zhang Weibing Yang Jun Tang Yuzhang Wu Bing Ni NKG2D+CD4+ T Cells Kill Regulatory T Cells in a NKG2D-NKG2D Ligand- Dependent Manner in Systemic Lupus Erythematosus
description	Abstract Systemic lupus erythematosus (SLE) features a decreased pool of CD4+CD25+Foxp3+ T regulatory (Treg) cells. We had previously observed NKG2D+CD4+ T cell expansion in contrast to a decreased pool of Treg cells in SLE patients, but whether NKG2D+CD4+ T cells contribute to the decreased Treg cells remains unclear. In the present study, we found that the NKG2D+CD4+ T cells efficiently killed NKG2D ligand (NKG2DL)+ Treg cells in vitro, whereby the surviving Treg cells in SLE patients showed no detectable expression of NKG2DLs. It was further found that MRL/lpr lupus mice have significantly increased percentage of NKG2D+CD4+ T cells and obvious decreased percentage of Treg cells, as compared with wild-type mice. Adoptively transferred NKG2DL+ Treg cells were found to be efficiently killed in MRL/lpr lupus mice, with NKG2D neutralization remarkably attenuating this killing. Anti-NKG2D or anti-interferon-alpha receptor (IFNAR) antibodies treatment in MRL/lpr mice restored Treg cells numbers and markedly ameliorated the lupus disease. These results suggest that NKG2D+CD4+ T cells are involved in the pathogenesis of SLE by killing Treg cells in a NKG2D-NKG2DL-dependent manner. Targeting the NKG2D-NKG2DL interaction might be a potential therapeutic strategy by which Treg cells can be protected from cytolysis in SLE patients.
format	article
author	Di Yang Zhiqiang Tian Mengjie Zhang Weibing Yang Jun Tang Yuzhang Wu Bing Ni
author_facet	Di Yang Zhiqiang Tian Mengjie Zhang Weibing Yang Jun Tang Yuzhang Wu Bing Ni
author_sort	Di Yang
title	NKG2D+CD4+ T Cells Kill Regulatory T Cells in a NKG2D-NKG2D Ligand- Dependent Manner in Systemic Lupus Erythematosus
title_short	NKG2D+CD4+ T Cells Kill Regulatory T Cells in a NKG2D-NKG2D Ligand- Dependent Manner in Systemic Lupus Erythematosus
title_full	NKG2D+CD4+ T Cells Kill Regulatory T Cells in a NKG2D-NKG2D Ligand- Dependent Manner in Systemic Lupus Erythematosus
title_fullStr	NKG2D+CD4+ T Cells Kill Regulatory T Cells in a NKG2D-NKG2D Ligand- Dependent Manner in Systemic Lupus Erythematosus
title_full_unstemmed	NKG2D+CD4+ T Cells Kill Regulatory T Cells in a NKG2D-NKG2D Ligand- Dependent Manner in Systemic Lupus Erythematosus
title_sort	nkg2d+cd4+ t cells kill regulatory t cells in a nkg2d-nkg2d ligand- dependent manner in systemic lupus erythematosus
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/2514c9158e8249eca56a54d544dcbea3
work_keys_str_mv	AT diyang nkg2dcd4tcellskillregulatorytcellsinankg2dnkg2dliganddependentmannerinsystemiclupuserythematosus AT zhiqiangtian nkg2dcd4tcellskillregulatorytcellsinankg2dnkg2dliganddependentmannerinsystemiclupuserythematosus AT mengjiezhang nkg2dcd4tcellskillregulatorytcellsinankg2dnkg2dliganddependentmannerinsystemiclupuserythematosus AT weibingyang nkg2dcd4tcellskillregulatorytcellsinankg2dnkg2dliganddependentmannerinsystemiclupuserythematosus AT juntang nkg2dcd4tcellskillregulatorytcellsinankg2dnkg2dliganddependentmannerinsystemiclupuserythematosus AT yuzhangwu nkg2dcd4tcellskillregulatorytcellsinankg2dnkg2dliganddependentmannerinsystemiclupuserythematosus AT bingni nkg2dcd4tcellskillregulatorytcellsinankg2dnkg2dliganddependentmannerinsystemiclupuserythematosus
_version_	1718388691882213376

NKG2D+CD4+ T Cells Kill Regulatory T Cells in a NKG2D-NKG2D Ligand- Dependent Manner in Systemic Lupus Erythematosus

Ejemplares similares