Impact on Experimental Colitis of Vitamin D Receptor Deletion in Intestinal Epithelial or Myeloid Cells

Inflammatory bowel diseases are gastrointestinal diseases that include Crohn disease and ulcerative colitis. The chronic inflammation is thought to result from an excessive inflammatory response to environmental factors such as luminal bacteria in genetically predisposed individuals. Studies have revealed that mice with impaired vitamin D signaling are more susceptible to experimental colitis. To better understand the contribution of vitamin D signaling in different cells of the gut to this disease, we investigated the effects of intestinal-specific or myeloid vitamin D receptor deletion. Our study addressed the importance of vitamin D receptor expression in intestinal epithelial cells using intestine-specific vitamin D receptor null mice and the contribution of vitamin D receptor expression in macrophages and granulocytes using myeloid-specific vitamin D receptor null mice in a dextran sodium sulfate model for experimental colitis. Loss of intestinal vitamin D receptor expression had no substantial effect on the clinical parameters of colitis and did not manifestly change mucosal cytokine expression. Inactivation of the vitamin D receptor in macrophages and granulocytes marginally affected colitis-associated symptoms but resulted in increased proinflammatory cytokine and increased beta-defensin-1 expression in the colon descendens of mice with colitis. Intestinal deletion of the vitamin D receptor did not aggravate symptoms of chemically induced colitis. Loss of the vitamin D receptor in macrophages and granulocytes mildly affected colitis-associated symptoms but greatly increased proinflammatory cytokine expression in the inflamed colon, suggesting a prominent role for innate immune cell vitamin D signaling in controlling gut inflammation.