Autoantibody Responses to Apolipoprotein A-I Are Not Diet- or Sex-Linked in C57BL/6 Mice.
Autoantibody Responses to Apolipoprotein A-I Are Not Diet- or Sex-Linked in C57BL/6 Mice.
复制标题
DOI：
10.4049/immunohorizons.2000027
复制
发表时间：
2020-08-05
期刊：
影响因子：
--
通讯作者：
Venditto VJ
中科院分区：
文献类型：
--
作者：
Pitts MG;Nardo D;Isom CM;Venditto VJ
动脉粥样硬化是造成全世界很大比例全因死亡率的原因，但它现在才开始被理解为一个复杂的疾病过程，涉及代谢损伤、慢性炎症和多种免疫机制。针对载脂蛋白A-I （ApoA-I）的抗体已在心血管疾病、自身免疫性疾病以及无这两种疾病病史的患者中发现。然而，对于这些腹肌是如何产生的，以及它们与饮食和性的关系，人们知之甚少。在目前的研究中，我们利用抗apoa - 1免疫对雄性和雌性C57BL/6小鼠进行建模。出乎意料的是，我们发现针对ApoA-I蛋白中单个先前未知的表位的自身抗体在小鼠中与免疫状态或血脂异常无关。随着时间的推移，我们分析了总IgG亚类，我们观察到，在雄性小鼠中，西方饮食的消耗抑制了IgG2b和IgG2c的年龄依赖性增加，而不是推动炎症性IgG亚类的增加。在雌性小鼠中观察到的缺乏变化表明，饮食和性别可能在Th1/Th2平衡中共同发挥作用，并最终在对病原体挑战的免疫中发挥作用。该报告表明，有必要将两性纳入与饮食和衰老有关的研究，并建议进一步研究apoa - 1中存在的免疫原性表位是有必要的。
Atherosclerosis is responsible for a large percentage of all-cause mortality worldwide, but it is only now beginning to be understood as a complex disease process involving metabolic insult, chronic inflammation, and multiple immune mechanisms. Abs targeting apolipoprotein A-I (ApoA-I) have been found in patients with cardiovascular disease, autoimmune conditions, as well as those with no documented history of either. However, relatively little is known about how these Abs are generated and their relationship to diet and sex. In the current study, we modeled this aspect of autoimmunity using anti–ApoA-I immunization of male and female C57BL/6 mice. Unexpectedly, we found that autoantibodies directed against a single, previously unknown, epitope within the ApoA-I protein developed irrespective of immunization status or dyslipidemia in mice. When total IgG subclasses were analyzed over the course of time, we observed that rather than driving an increase in inflammatory IgG subclasses, consumption of Western diet suppressed age-dependent increases in IgG2b and IgG2c in male mice only. The lack of change observed in female mice suggested that diet and sex might play a combined role in Th1/Th2 balance and, ultimately, in immunity to pathogen challenge. This report demonstrates the need for inclusion of both sexes in studies pertaining to diet and aging and suggests that further study of immunogenic epitopes present in ApoA-I is warranted.