Vitamin D receptor is required to control gastrointestinal immunity in IL-10 knockout mice
Article first published online: 13 FEB 2006
Volume 117, Issue 3, pages 310–318, March 2006
How to Cite
Froicu, M., Zhu, Y. and Cantorna, M. T. (2006), Vitamin D receptor is required to control gastrointestinal immunity in IL-10 knockout mice. Immunology, 117: 310–318. doi: 10.1111/j.1365-2567.2005.02290.x
- Issue published online: 13 FEB 2006
- Article first published online: 13 FEB 2006
- Received 22 August 2005; revised 25 September 2005; accepted 28 September 2005.
- inflammatory bowel disease;
- T cells;
- vitamin D receptors
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-γ, IL-1β, tumour necrosis factor-α 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.