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[摘要]：BACKGROUND & AIMS: Retinoic acid plays a positive role in induction of FoxP3(+) regulatory T cells. Because retinoic acid is produced as a metabolite of vitamin A in the intestine and FoxP3(+) T cells regulate intestinal inflammation, we investigated the impact of vitamin A status on the regulatory T cells and inflammation in the intestine. METHODS: The SAMP1/YP model is a Mouse model of Crohn's disease. We made vitamin A-deficient, vitamin A-excessive, and normal SAMP1/YP mice and assessed the intestinal inflammation. We also investigated the phenotype and Function of FoxP3(+) T cells induced in different levels of vitamin A availability in regulation of intestinal inflammation in a T-cell-induced inflammation model in SCID mice. RESULTS: The limited and excessive vitamin A conditions induced distinct FoxP3(+) T-cell subsets in vivo, and both ameliorated the intestinal inflammation in SAMP1/YP mice. The limited vitamin A condition greatly induced unusual CD103(+)CCR7(+) FoxP3(+) cells, while the high vitamin A condition induced CCR9(+)alpha 4p7(+) FoxP3(+) T cells in the intestine. Both FoxP3(+) T-cell populations, when transferred into mice with ongoing intestinal inflammation, were highly effective in reversing the inflammation. Blockade or lack of occupancy of RAR alpha is a mechanism to induce highly suppressive CD103(+)CCR7(+) FoxP3(+) cells in both the thymus and periphery in limited vitamin A availability. CONCLUSIONS: Our results identify novel pathways of inducing highly suppressive FoxP3(+) regulatory T cells that can effectively control intestinal inflammation. The results have significant ramifications in treating inflammatory bowel diseases. |
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