IL-21 Is a Double-Edged Sword in the Systemic Lupus Erythematosus-like Disease of BXSB.Yaa Mice

被引：46

作者：

McPhee, Caroline G. ^{[1
]}

Bubier, Jason A. ^{[1
]}

Sproule, Thomas J. ^{[1
]}

Park, Giljun ^{[1
]}

Steinbuck, Martin P. ^{[1
]}

Schott, William H. ^{[1
]}

Christianson, Gregory J. ^{[1
]}

Morse, Herbert C., III ^{[2
]}

Roopenian, Derry C. ^{[1
]}

机构：

[1] Jackson Lab, Bar Harbor, ME 04609 USA

[2] NIAID, Lab Immunogenet, NIH, Rockville, MD 20852 USA

来源：

JOURNAL OF IMMUNOLOGY | 2013年 / 191卷 / 09期

基金：

美国国家卫生研究院;

关键词：

HELPER T-CELLS; GERMINAL CENTER RESPONSES; B-CELLS; BCL-6; EXPRESSION; MURINE LUPUS; YAA MICE; AUTOIMMUNITY; INTERLEUKIN-21; GENERATION; RECEPTOR;

D O I：

10.4049/jimmunol.1300439

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The pleiotropic cytokine IL-21 is implicated in the pathogenesis of human systemic lupus erythematosus by polymorphisms in the molecule and its receptor (IL-21R). The systemic lupus erythematosus-like autoimmune disease of BXSB.Yaa mice is critically dependent on IL-21 signaling, providing a model for understanding IL-21/IL-21R signaling in lupus pathogenesis. In this study, we generated BXSB.Yaa mice selectively deficient in IL-21R on B cells, on all T cells, or on CD8(+) T cells alone and examined the effects on disease. We found that IL-21 signaling to B cells is essential for the development of all classical disease manifestations, but that IL-21 signaling also supports the expansion of central memory, CD8(+) suppressor cells and broadly represses the cytokine activity of CD4(+) T cells. These results indicate that IL-21 has both disease-promoting and disease-suppressive effects in the autoimmune disease of BXSB.Yaa mice.

引用

页码：4581 / 4588

页数：8

共 47 条

[1] Customized molecular phenotyping by quantitative gene expression and pattern recognition analysis [J].