Autophagy impairment in liver CD11c(+) cells promotes non-alcoholic fatty liver disease through production of IL-23.
Autophagy impairment in liver CD11c(+) cells promotes non-alcoholic fatty liver disease through production of IL-23.
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DOI：
10.1038/s41467-022-29174-y
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发表时间：
2022-03-17
影响因子：
16.6
通讯作者：
Akbari O
中科院分区：
文献类型：
--
作者：
Galle-Treger L;Helou DG;Quach C;Howard E;Hurrell BP;Muench GRA;Shafiei-Jahani P;Painter JD;Iorga A;Dara L;Emamaullee J;Golden-Mason L;Rosen HR;Soroosh P;Akbari O
肥胖率在全球范围内上升，同时非酒精性脂肪性肝病(NAFLD)也在流行。自噬是细胞物质降解的重要机制，在维持肝脏内环境平衡中起着重要作用。在这里，我们探讨了自噬相关5(ATG5)缺乏对饲喂HFD的小鼠肝脏CD11c+细胞的影响。与对照组小鼠相比，ATG5缺陷的CD11c+小鼠表现出葡萄糖耐量增加和胰岛素敏感性降低。这种表型与NAFLD的发生有关。我们观察到，HFD喂养后，肝脏CD11c+髓系细胞分泌IL-23。我们证明，治疗性和预防性的IL-23阻断都可以减轻葡萄糖耐量、胰岛素抵抗，并防止NAFLD的发展。本研究揭示了自噬和肝脏CD11c+细胞产生IL-23在NAFLD发病机制中的作用，并提出了潜在的治疗靶点。自噬的功能及其对非酒精性脂肪性肝病的影响尚不完全清楚。在这里，作者表明，在CD11c+细胞自噬途径被定向破坏的小鼠中，涉及IL-23的NAFLD的发展加速，而阻断IL-23可以减少疾病。
There has been a global increase in rates of obesity with a parallel epidemic of non-alcoholic fatty liver disease (NAFLD). Autophagy is an essential mechanism involved in the degradation of cellular material and has an important function in the maintenance of liver homeostasis. Here, we explore the effect of Autophagy-related 5 (Atg5) deficiency in liver CD11c+ cells in mice fed HFD. When compared to control mice, Atg5-deficient CD11c+ mice exhibit increased glucose intolerance and decreased insulin sensitivity when fed HFD. This phenotype is associated with the development of NAFLD. We observe that IL-23 secretion is induced in hepatic CD11c+ myeloid cells following HFD feeding. We demonstrate that both therapeutic and preventative IL-23 blockade alleviates glucose intolerance, insulin resistance and protects against NAFLD development. This study provides insights into the function of autophagy and IL-23 production by hepatic CD11c+ cells in NAFLD pathogenesis and suggests potential therapeutic targets. The function of autophagy and how this affects non-alcoholic fatty liver disease is not fully known. Here the authors show that in mice with a targeted disruption of the autophagy pathway in CD11c+ cells, development of NAFLD is accelerated involving IL-23 and blocking of IL-23 reduces disease.
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CRL4(DCAF2) 负向调节树突状细胞中 IL-23 的产生并限制银屑病的发展
DOI：
10.1084/jem.20180210
发表时间：
2018-08-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Huang T;Gao Z;Zhang Y;Fan K;Wang F;Li Y;Zhong J;Fan HY;Cao Q;Zhou J;Xiao Y;Hu H;Jin J
通讯作者：
Jin J
影响因子：
16.6
作者：
Galle-Treger, Lauriane;Sankaranarayanan, Ishwarya;Akbari, Omid
通讯作者：
Akbari, Omid
来自整个利什曼原虫抗原的鼻内疫苗可提供保护并诱导针对内脏利什曼病的特定免疫反应。
影响因子：
3.8
作者：
Helou DG;Mauras A;Fasquelle F;Lanza JS;Loiseau PM;Betbeder D;Cojean S
通讯作者：
Cojean S
IL-10产生的肠道巨噬细胞通过限制IL-23合成来防止过度的抗菌先天免疫。
影响因子：
16.6
作者：
Krause, Petra;Morris, Venetia;Greenbaum, Jason A.;Park, Yoon;Bjoerheden, Unni;Mikulski, Zbigniew;Muffley, Tracy;Shui, Jr-Wen;Kim, Gisen;Cheroutre, Hilde;Liu, Yun-Cai;Peters, Bjoern;Kronenberg, Mitchell;Murai, Masako
通讯作者：
Murai, Masako
影响因子：
4.5
作者：
Kotze PG;Ma C;Almutairdi A;Panaccione R
通讯作者：
Panaccione R