NKG2D(+)CD4(+) T Cells Kill Regulatory T Cells in a NKG2D-NKG2D Ligand- Dependent Manner in Systemic Lupus Erythematosus.
NKG2D(+)CD4(+) T Cells Kill Regulatory T Cells in a NKG2D-NKG2D Ligand- Dependent Manner in Systemic Lupus Erythematosus.
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NKG2D( ) CD4( ) T 细胞在系统性红斑狼疮中以 NKG2D-NKG2D 配体依赖性方式杀死调节性 T 细胞
DOI：
10.1038/s41598-017-01379-y
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发表时间：
2017-04-28
影响因子：
4.6
通讯作者：
Ni B
中科院分区：
文献类型：
--
作者：
Yang D;Tian Z;Zhang M;Yang W;Tang J;Wu Y;Ni B
系统性红斑狼疮 (SLE) 的特点是 CD4+CD25+Foxp3+ T 调节 (Treg) 细胞池减少。我们之前观察到 SLE 患者中 NKG2D+CD4+ T 细胞扩增，而 Treg 细胞池减少，但 NKG2D+CD4+ T 细胞是否导致 Treg 细胞减少仍不清楚。在本研究中，我们发现NKG2D + CD4 + T细胞在体外有效杀死NKG2D配体（NKG2DL）+ Treg细胞，因此SLE患者中存活的Treg细胞未检测到NKG2DL的表达。进一步发现，与野生型小鼠相比，MRL/lpr狼疮小鼠NKG2D+CD4+T细胞比例明显升高，Treg细胞比例明显下降。研究发现，过继转移的 NKG2DL+ Treg 细胞在 MRL/lpr 狼疮小鼠中被有效杀死，而 NKG2D 中和可显着减弱这种杀伤作用。对 MRL/lpr 小鼠进行抗 NKG2D 或抗干扰素 α 受体 (IFNAR) 抗体治疗可恢复 Treg 细胞数量，并显着改善狼疮疾病。这些结果表明NKG2D+CD4+ T细胞通过以NKG2D-NKG2DL依赖的方式杀死Treg细胞参与SLE的发病机制。针对 NKG2D-NKG2DL 相互作用可能是一种潜在的治疗策略，通过该策略可以保护 SLE 患者的 Treg 细胞免受细胞溶解。
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.