Brown Chrysothemis C, Noelle Randolph J
Division of Transplantation Immunology and Mucosal Biology, Kings College London, United Kingdom.
Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Norris Cotton Cancer Center, Lebanon, NH, USA.
Eur J Immunol. 2015 May;45(5):1287-95. doi: 10.1002/eji.201344398.
The importance of vitamin A for host defense is undeniable and the study of its mechanisms is paramount. Of the estimated 250 million preschool children who are vitamin A-deficient (VAD), 10% will die from their increased susceptibility to infectious disease. Vitamin A supplementation was established in the 1980s as one of the most successful interventions in the developing world. Understanding how vitamin A controls immunity will help curb the mortality and morbidity associated with vitamin A deficiency and exploit the immune-enhancing capacity of vitamin A to heighten host resistance to infectious disease. The discoveries that retinoic acid (RA) imprints the homing of leukocytes to the gut and enhances the induction of regulatory T cells, highlighted a potential role for RA in mucosal tolerance. However, more recently emerging data tell of a more profound systemic impact of RA on leukocyte function and commitment. In animal models using genetic manipulation of RA signaling, we learned when and how RA controls T cell fate. Here, we review the role for RA as a critical checkpoint regulator in the differentiation of CD4(+) T cells within the immune system.
维生素A对宿主防御的重要性是不可否认的，对其作用机制的研究至关重要。据估计，在2.5亿学龄前维生素A缺乏（VAD）儿童中，10%会因对传染病易感性增加而死亡。维生素A补充剂在20世纪80年代被确立为发展中国家最成功的干预措施之一。了解维生素A如何控制免疫将有助于降低与维生素A缺乏相关的死亡率和发病率，并利用维生素A的免疫增强能力提高宿主对传染病的抵抗力。视黄酸（RA）可促使白细胞归巢至肠道并增强调节性T细胞的诱导，这一发现凸显了RA在黏膜耐受中的潜在作用。然而，最近出现的数据表明，RA对白细胞功能和定向有着更深远的系统性影响。在使用RA信号通路基因操作的动物模型中，我们了解到RA何时以及如何控制T细胞命运。在此，我们综述RA作为免疫系统中CD4(+) T细胞分化关键检查点调节因子的作用。
