Liver X receptors (LXRs) are regulators of cholesterol metabolism that also modulate immune responses. Inactivation of LXR α and β in mice leads to autoimmunity; however, how the regulation of cholesterol metabolism contributes to autoimmunity is unclear. Here we found that cholesterol loading of CD11c+ cells triggered the development of autoimmunity, whereas preventing excess lipid accumulation by promoting cholesterol efflux was therapeutic. LXRβ-deficient mice crossed to the hyperlipidemic ApoE-deficient background or challenged with a high-cholesterol diet developed autoantibodies. Cholesterol accumulation in lymphoid organs promoted T cell priming and stimulated the production of the B cell growth factors Baff and April. Conversely, B cell expansion and the development of autoantibodies in ApoE/LXR-β-deficient mice was reversed by ApoA-I expression. These findings implicate cholesterol imbalance as a contributor to immune dysfunction and suggest that stimulating HDL-dependent reverse cholesterol transport could be beneficial in the setting of autoimmune disease.

译文

肝X受体 (lxr) 是胆固醇代谢的调节剂,也调节免疫反应。小鼠LXR α 和 β 的失活导致自身免疫; 然而,胆固醇代谢的调节如何促进自身免疫尚不清楚。在这里,我们发现CD11c细胞的胆固醇负载触发了自身免疫的发展,而通过促进胆固醇流出来防止过多的脂质积累是有治疗作用的。Lxr β 缺陷型小鼠杂交到高脂血症性ApoE缺陷型背景或以高胆固醇饮食攻击产生了自身抗体。淋巴器官中的胆固醇积累促进了T细胞的启动,并刺激了b细胞生长因子Baff和4月的产生。相反,ApoA-I表达逆转了ApoE/LXR-β 缺陷小鼠中的b细胞扩增和自身抗体的发展。这些发现暗示胆固醇失衡是导致免疫功能障碍的原因,并表明刺激HDL依赖性胆固醇反向转运可能对自身免疫性疾病的发生有益。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录