A requirement for early neonatal exposure to vitamin D for iNKT cells (134.26)

Abstract

Abstract CD1d-reactive invariant natural killer T (iNKT) cells are a unique subset of lymphocytes, which play important roles in immune regulation. We have shown that the vitamin D receptor (VDR) is required for the development of iNKT cells. Here we determined the effect of the vitamin D ligand (calcitriol) on iNKT cells. Like the VDR KO mice fewer iNKT cells were identified in the calcitriol deficient mice. However, ligand deficiency did not affect the function of the remaining iNKT cells. In addition, calcitirol deficiency did not affect the development of iNKT cells in the thymus, while VDR KO iNKT cells were blocked at the CD44+/NK1.1- stage of development. The 1alpha-hydroxylase (encoded by cyp27B1) is an enzyme required for production of calcitriol. Cyp27B1 KO mice are calcitriol deficient because they cannot convert vitamin D to the active form. Cyp27B1 ko/+ breeders were fed vitamin D deficient diets. At three weeks of age WT and Cyp27B1 KO littermates were weaned and fed diets that contain vitamin D for the next 5 weeks. Analysis of iNKT cells from these mice showed that both the WT and Cyp27B1 KO littermates had very few iNKT cells. In fact the percentage of iNKT cells in the liver of vitamin D deficient mice littermates were very low 1.2-1.8% and lower than in the VDR KO mice (6%). Early exposure to calcitriol in utero is required for iNKT cell development and iNKT cells failed to recover in either WT or Cyp27B1 KO littermates that were calcitriol sufficient from the age of 5-8 wks. The data show that there are differences in the role of the VDR and the vitamin D ligand on iNKT cells. In addition, the data suggest a critical role for calcitriol early either during neonatal development or the first 3 weeks post-birth in inducing iNKT cells.