Yu Sanhong, Cantorna Margherita T
Department of Veterinary and Biomedical Sciences, Immunobiology Graduate Program, Center for Molecular Immunology and Infectious Diseases, Pennsylvania State University, University Park, PA 16802, USA.
Proc Natl Acad Sci U S A. 2008 Apr 1;105(13):5207-12. doi: 10.1073/pnas.0711558105. Epub 2008 Mar 25.
CD1d-reactive natural killer T (NKT) cells with an invariant T cell receptor Valpha14 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 nutrient/hormone that has been shown to regulate conventional T cell responses but not T cell development. The data show that 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. VDR KO iNKT cells fail to express NK1.1, although they express normal levels of CD122. Extrinsic factors that impact iNKT cell development and function in VDR KO mice include 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. In addition, VDR KO iNKT cells were intrinsically defective even when WT antigen-presenting cells were used to stimulate them.
具有恒定T细胞受体Valpha14重排的CD1d反应性自然杀伤T（NKT）细胞是淋巴细胞的一个独特亚群，在免疫调节、肿瘤监测和宿主抵御病原体方面发挥重要作用。维生素D是一种营养素/激素，已被证明可调节传统T细胞反应，但不影响T细胞发育。数据表明，维生素D受体（VDR）的表达是iNKT细胞正常发育和功能所必需的。来自VDR基因敲除小鼠的iNKT细胞存在内在缺陷，且缺乏T-bet表达。VDR基因敲除的iNKT细胞虽然表达正常水平的CD122，但无法表达NK1.1。影响VDR基因敲除小鼠中iNKT细胞发育和功能的外在因素包括肝脏无法支持稳态增殖以及胸腺中CD1d和其他对胸腺中最佳抗原呈递重要的因子表达降低。此外，即使使用野生型抗原呈递细胞刺激，VDR基因敲除的iNKT细胞仍存在内在缺陷。
