Abstract
CD1d-reactive natural killer T (NKT) cells with an invariant T cell receptor Vα14 rearrangement (i) are a unique subset of lymphocytes, which play important roles in immune regulation, tumor surveillance and host defense against pathogens. Vitamin D and the vitamin D receptor (VDR) are important regulators of T cell function, yet their role in iNKT cells remains unknown. Expression of the vitamin D receptor (VDR) is required for normal development of iNKT cells. Mice lacking the VDR had significantly fewer iNKT cells and the remaining iNKT cells were hyporesponsive. iNKT cell development is blocked at a late stage in iNKT cell development, the CD44high NK1.1− stage. Bone marrow transplantation showed that VDR knockout (KO) hematopoetic cells fail to repopulate iNKT cells in the wild type thymus. The block was not due to fewer iNKT precursors in the VDR KO mice but instead CD1d expression was diminished in the VDR KO thymus. The decreased CD1d results in fewer, hyporesponsive iNKT cells in the VDR KO mouse. The data suggest that vitamin D through the vitamin D receptor is critical for proper iNKT cell development and function.