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Submitted on July 17, 2003
Accepted on September 10, 2003
1 Department of Nutrition, 126 S. Henderson Bldg., University Park, PA 16802; Immunopathogenesis Section, NIAID, NIH, 50 South Dr. MSC 8003, RM 6154, Bethesda, MD 20892; and Department of Biology, Notre Dame University, South Bend, IN.
* To whom correspondence should be addressed. E-mail: mxc69{at}psu.edu.
The active form of vitamin D (1,25D3) suppressed the development of animal models of human autoimmune diseases including experimental inflammatory bowel disease (IBD). The vitamin D receptor (VDR) is required for all known biologic effects of vitamin D. Here we show that VDR deficiency (knockout, KO) resulted in severe inflammation of the gastrointestinal tract in two different experimental models of IBD. In the CD45RB transfer model of IBD, CD4+/CD45RBhigh T cells from VDR KO mice induced more severe colitis than WT CD4+/CD45RBhigh T cells. The second model of IBD used was the spontaneous colitis that develops in interleukin (IL)-10 KO mice. VDR/IL-10 double KO mice developed accelerated IBD and 100% mortality by 8 weeks of age. At 8 weeks of age all of the VDR and IL10 single KO mice were healthy. Rectal bleeding was observed in every VDR/IL-10 KO mouse. Splenocytes from the VDR/IL10 double KO mice cells transferred IBD symptoms. The severe IBD in VDR/IL10 double KO mice is a result of the immune system and not as a result of altered calcium homeostasis, or gastrointestinal tract function. The data establishes an essential role for VDR signaling in the regulation of inflammation in the gastrointestinal tract.
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