STAT4 deficiency reduces autoantibody production and glomerulonephritis in a mouse model of lupus
- 作者：Zhiwei Xu ; Biyan Duan ; Byron P. Croker and Laurence Morel
- 关键词：Lupus ; Cytokines ; Mouse models ; Autoantibodies ; Glomerulonephritis ; IL-12 ; IL-4
- 刊名：Clinical Immunology
- 出版年：2006
- 期刊代码：95_15216616
- 类别：imm
- 出版时间：August 2006
- 卷：120
- 期：2
- 页码：189-198
- 文件大小：681 K
摘要
To determine the respective role of the IL-12 and IL-4 pathways in the pathogenesis of systemic lupus erythematosus, we bred the Stat4 and Stat6 null alleles onto the lupus-prone mouse B6.TC, which is a congenic derivative of NZM2410. This model is characterized by abnormal splenocyte expansion, distribution and architecture, T cell activation, peripheral B cell development, production of anti-nuclear antibodies, and proliferative glomerulonephritis. STAT4 deficiency normalized the expression of each of these disease markers toward or to C57BL/6 levels. In contrast, STAT6 deficiency impacted splenocyte expansion and architecture, T cell activation, and anti-nuclear autoantibody production, but without any significant effect on B cell development or renal pathology. These results show that the IL-12/STAT4 pathway is involved in multiple disease-associated phenotypes in the B6.TC mouse. In contrast, the IL-4/STAT6 pathway regulates only a subset of disease markers that did not affect renal pathology.