Posttranscriptional regulation of Il10 gene expression allows natural killer cells to express immunoregulatory function

被引：149

作者：

Maroof, Asher ^{[1
,2
]}

Beattie, Lynette ^{[1
,2
]}

Zubairi, Soombul ^{[1
,2
]}

Svensson, Mattias ^{[1
,2
]}

Stager, Simona ^{[1
,2
]}

Kaye, Paul M. ^{[1
,2
]}

机构：

[1] Univ York, Hull York Med Sch, Immunol & Infect Unit, York YO10 5YW, N Yorkshire, England

[2] Univ York, Dept Biol, York YO10 5YW, N Yorkshire, England

来源：

IMMUNITY | 2008年 / 29卷 / 02期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

D O I：

10.1016/j.immuni.2008.06.012

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Natural killer (NK) cells play a well-recognized role in early pathogen containment and in shaping acquired cell-mediated immunity. However, indirect evidence in humans and experimental models has suggested that NK cells also play negative regulatory roles during chronic disease. To formally test this hypothesis, we employed a well-defined experimental model of visceral leishmaniasis. Our data demonstrated that NKp46(+)CD49b(+)CD3(-) NK cells were recruited to the spleen and into hepatic granulomas, where they inhibited host protective immunity in an interleukin-10 (IL-10)-dependent manner. Although IL-10 mRNA could be detected in activated NK cells 24 hr after infection, the inhibitory function of NK cells was only acquired later during infection, coincident with increased IL-10 mRNA stability and an enhanced capacity to secrete IL-10 protein. Our data support a growing body of literature that implicates NK cells as negative regulators of cell-mediated immunity and suggest that NK cells, like CD4(+) T helper 1 cells, may acquire immunoregulatory functions as a consequence of extensive activation.

引用

页码：295 / 305

页数：11

共 71 条

[61] Both interleukin-4 (IL-4) and IL-4 receptor α signaling contribute to the development of hepatic granulomas with optimal antileishmanial activity [J].