CD1d-dependent rewiring of lipid metabolism in macrophages regulates innate immune responses.
CD1d-dependent rewiring of lipid metabolism in macrophages regulates innate immune responses.
复制标题
DOI：
10.1038/s41467-022-34532-x
复制
发表时间：
2022-11-07
影响因子：
16.6
通讯作者：
Barral, Patricia
中科院分区：
文献类型：
--
作者：
Brailey, Phillip M.;Evans, Lauren;Lopez-Rodriguez, Juan Carlos;Sinadinos, Anthony;Tyrrel, Victoria;Kelly, Gavin;O'Donnell, Valerie;Ghazal, Peter;John, Susan;Barral, Patricia
细胞代谢的改变是巨噬细胞激活的基础，但关于关键免疫分子如何调节巨噬细胞代谢程序的了解甚少。在这里，我们揭示了抗原呈递分子CD1d在脂质代谢控制中的功能。我们发现cd1缺陷的巨噬细胞表现出代谢重编程，脂质代谢途径下调，外源性脂质进口增加。由于CD1d-KO细胞在toll样受体刺激下表现出更高的信号传导和细胞因子分泌，这种代谢重组使巨噬细胞对先天信号的反应增强。在机制上，CD1d通过控制脂质转运体CD36的内化来调节脂质进口，而通过CD36阻断脂质摄取可恢复巨噬细胞的代谢和免疫反应。因此，我们的数据显示CD1d是巨噬细胞炎症代谢回路的关键调节因子，独立于其控制T细胞反应的功能。代谢途径的调节与包括巨噬细胞在内的免疫细胞的调节有关。在这里，作者确定了CD1d在巨噬细胞代谢重组中的作用，这改变了对先天刺激的反应。
Alterations in cellular metabolism underpin macrophage activation, yet little is known regarding how key immunological molecules regulate metabolic programs in macrophages. Here we uncover a function for the antigen presenting molecule CD1d in the control of lipid metabolism. We show that CD1d-deficient macrophages exhibit a metabolic reprogramming, with a downregulation of lipid metabolic pathways and an increase in exogenous lipid import. This metabolic rewiring primes macrophages for enhanced responses to innate signals, as CD1d-KO cells show higher signalling and cytokine secretion upon Toll-like receptor stimulation. Mechanistically, CD1d modulates lipid import by controlling the internalization of the lipid transporter CD36, while blocking lipid uptake through CD36 restores metabolic and immune responses in macrophages. Thus, our data reveal CD1d as a key regulator of an inflammatory-metabolic circuit in macrophages, independent of its function in the control of T cell responses. Modulation of metabolic pathways is linked to regulation of immune cells including macrophages. Here the authors identify a role for CD1d in the metabolic rewiring of macrophages, which alters responsiveness to innate stimuli.
登录
查看更多内容
影响因子：
14.9
作者：
Gene Ontology Consortium
通讯作者：
Gene Ontology Consortium
影响因子：
8.8
作者：
Feng, William W.;Wilkins, Owen;Kurokawa, Manabu
通讯作者：
Kurokawa, Manabu
影响因子：
32.4
作者：
Blanc M;Hsieh WY;Robertson KA;Kropp KA;Forster T;Shui G;Lacaze P;Watterson S;Griffiths SJ;Spann NJ;Meljon A;Talbot S;Krishnan K;Covey DF;Wenk MR;Craigon M;Ruzsics Z;Haas J;Angulo A;Griffiths WJ;Glass CK;Wang Y;Ghazal P
通讯作者：
Ghazal P
DOI：
10.15252/embj.201797537
发表时间：
2018-03-01
期刊：
The EMBO journal
影响因子：
--
作者：
Sáez de Guinoa J;Jimeno R;Gaya M;Kipling D;Garzón MJ;Dunn-Walters D;Ubeda C;Barral P
通讯作者：
Barral P
DOI：
10.1016/j.metabol.2020.154338
发表时间：
2021-01
期刊：
Metabolism: clinical and experimental
影响因子：
--
作者：
Christofides A;Konstantinidou E;Jani C;Boussiotis VA
通讯作者：
Boussiotis VA