Murine CD8+T cells but not macrophages express the vitamin D 1 alpha-hydroxylase

作者：Ooi Jot Hui; McDaniel Kaitlin L; Weaver Veronika; Cantorna Margherita T^*

来源：Journal of Nutritional Biochemistry, 2014, 25(1): 58-65.

DOI：10.1016/j.jnutbio.2013.09.003

• Vitamin D
• Cyp27B1
• T cells
• Inflammation

The active form of vitamin D, 1,25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3] is synthesized by the 1 alpha-hydroxylase, which is encoded by the Cyp27B1 gene. Using transgenic mice that have replaced the Cyp27B1 gene with the bacterial lacZ reporter gene (p-galactosidase), the inflammatory conditions that induce Cyp27B1 in the immune system were probed. A variety of stimuli including lipopolysaccharide, anti-CD3 or PMA/ionomycin were used to stimulate splenocytes and bone marrow derived macrophage in vitro. Only anti-CD3 stimulation resulted in a low induction of beta-galactosidase activity in the spleen, indicating that T cells might be a source of Cyp27B1. In vivo, challenge with lipopolysaccharide, alpha-galactosylceramide, and Listeria monocytogenes failed to induce beta-galactosidase activity outside of the kidneys. During more prolonged and severe inflammation there was staining in both the lungs and the gastrointestinal tract for beta-galactosidase. Furthermore, wild-type reconstitution of the hematopoietic cell population in Cyp27B1 KO mice protected the mice from experimental colitis. T cell production of Cyp27B1 activity was shown to be from the CD8+ but not the CD4+ T cell population. CD8+ T cells expressed the reporter gene only after 48 h of stimulation. The data is consistent with a model where CD8+ T cells are activated to produce Cyp27B1 and 1,25(OH)(2)D-3 that serves to turn off the local immune response.

• 出版日期2014-1