Vitamin D receptor is required to control gastrointestinal immunity in IL-10 knockout mice

被引:114
|
作者
Froicu, M
Zhu, Y
Cantorna, MT
机构
[1] Penn State Univ, Dept Nutr Sci, Immunol Res Lab, Pathobiol Grad Program, University Pk, PA 16802 USA
[2] Penn State Univ, Immunol Res Labs, Pathobiol Grad Program, Dept Vet Sci, University Pk, PA 16802 USA
[3] Penn State Univ, Dept Nutr Sci, Immunol Res Lab, Nutr Grad Program, University Pk, PA 16802 USA
[4] Penn State Univ, Dept Vet Sci, Immunol Res Lab, Nutr Grad Program, University Pk, PA 16802 USA
关键词
inflammatory bowel disease; mice; T cells; vitamin D receptors;
D O I
10.1111/j.1365-2567.2005.02290.x
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 vitamin D receptor (VDR) is a nuclear receptor expressed in a number of different cells of the immune system. This study was performed to determine the effect of VDR deficiency on immune function and inflammation of the gastrointestinal tract in a model of inflammatory bowel disease, namely interleukin-10 (IL-10) knockout mice. IL-10 knockout mice were generated which either could or could not respond to vitamin D (double IL-10/VDR knockout; DKO). The distribution and function of lymphocytes in both the primary and secondary lymphoid organs were compared and determined as a function of the severity of intestinal inflammation. DKO mice had normal thymic development and peripheral T-cell numbers at 3 weeks of age, but a week after intestinal disease was detected the thymus was dysplastic with a reduction in cellularity. The atrophy was coupled with increased apoptosis. The spleen weight of DKO mice increased as a result of the accumulation of red blood cells; however, there was a 50% reduction in the numbers of T and B cells. Conversely, the mesenteric lymph nodes were enlarged and contained increased numbers of lymphocytes. The T cells from DKO mice were of a memory phenotype and were hyporesponsive to T-cell receptor stimulation. Colitis in the DKO mice was associated with local and high expression of IL-2, interferon-gamma, IL-1 beta, tumour necrosis factor-alpha and IL-12. The primary and secondary lymphoid organs in DKO mice are profoundly altered as a consequence of the fulminating inflammation in the gastrointestinal tract. VDR expression is required for the T cells and other immune cells to control inflammation in the IL-10 KO mice.
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页码:310 / 318
页数:9
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