Vitamin D receptor expression is required for the normal development and function of iNKT cells

Abstract

CD1d‐reactive natural killer T (NKT) cells with an invariant T cell receptor Vα14 rearrangement are a unique subset of lymphocytes, which play important roles in immune regulation, tumor surveillance and host defense against pathogens. Vitamin D is a potent regulator of conventional T cell development and function but there is no information on whether vitamin D regulates NKT cells. Expression of the vitamin D receptor (VDR) is required for normal development and function of iNKT cells. The iNKT cells from VDR KO mice are intrinsically defective and lack T‐bet expression that result in a population of immature NK1.1− iNKT cells that express normal levels of CD122. Bone marrow transplantation studies showed that non‐hematopoetic cell expression of the VDR was essential for intact iNKT cell responses. Extrinsic factors that impact iNKT cell development and function in the VDR KO mice included a failure of the liver to support homeostatic proliferation and reduced thymic expression of CD1d and other factors important for optimal antigen presentation in the thymus. VDR deficiency resulted in reduced thymic CD1d expression that impaired the ability of thymocytes but not peripheral DC to act as antigen presenting cells. The defects in VDR KO iNKT cells stem from both intrinsic and extrinsic requirement for VDR expression.