Yang Jun-Qi, Singh Avneesh K, Wilson Michael T, Satoh Minoru, Stanic Aleksandar K, Park Jang-June, Hong Seokmann, Gadola Stephan D, Mizutani Akiei, Kakumanu Srinivasa R, Reeves Westley H, Cerundolo Vincenzo, Joyce Sebastian, Van Kaer Luc, Singh Ram Raj
Department of Internal Medicine, Autoimmunity and Tolerance Laboratory, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
J Immunol. 2003 Aug 15;171(4):2142-53. doi: 10.4049/jimmunol.171.4.2142.
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that is accompanied by the emergence of autoreactive T cells and a reduction in regulatory T cells. Humans and mice with SLE have reduced numbers of CD1d-restricted NK T cells, suggesting a role for these cells in the regulation of SLE. In this study, we show that CD1d deficiency exacerbates lupus nephritis induced by the hydrocarbon oil pristane. This exacerbation in disease is associated with: 1) reduced TNF-alpha and IL-4 production by T cells, especially during the disease induction phase; and 2) expansion of marginal zone B cells. Strikingly, inoculation of pristane in wild-type mice resulted in reduced numbers and/or functions of NK T cells and CD1d-expressing dendritic cells. These findings suggest that CD1d may play an immunoregulatory role in the development of lupus in the pristane-induced model.
系统性红斑狼疮(SLE)是一种全身性自身免疫性疾病,伴有自身反应性T细胞的出现和调节性T细胞数量的减少。患有SLE的人类和小鼠中,CD1d限制性自然杀伤T细胞(NK T细胞)数量减少,提示这些细胞在SLE的调节中发挥作用。在本研究中,我们发现CD1d缺陷会加剧由烃油 pristane诱导的狼疮性肾炎。疾病的这种加剧与以下因素有关:1)T细胞产生的肿瘤坏死因子-α(TNF-α)和白细胞介素-4(IL-4)减少,尤其是在疾病诱导阶段;2)边缘区B细胞的扩增。值得注意的是,在野生型小鼠中接种pristane会导致NK T细胞和表达CD1d的树突状细胞数量减少和/或功能降低。这些发现表明,在pristane诱导的模型中,CD1d可能在狼疮的发展中发挥免疫调节作用。