The Peter Gorer Department of Immunobiology, King's College London, London, UK.
The Francis Crick Institute, London, UK.
Nat Commun. 2022 Nov 7;13(1):6723. doi: 10.1038/s41467-022-34532-x.
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.
细胞代谢的改变是巨噬细胞激活的基础，但对于关键免疫分子如何调节巨噬细胞中的代谢程序知之甚少。在这里，我们揭示了抗原呈递分子 CD1d 在控制脂质代谢中的作用。我们发现，缺乏 CD1d 的巨噬细胞表现出代谢重编程，脂质代谢途径下调，外源性脂质摄取增加。这种代谢重塑使巨噬细胞对先天信号做出增强的反应做好准备，因为 CD1d-KO 细胞在 Toll 样受体刺激时显示出更高的信号和细胞因子分泌。在机制上，CD1d 通过控制脂质转运蛋白 CD36 的内化来调节脂质摄取，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，我们的数据揭示了 CD1d 是巨噬细胞中炎症代谢回路的关键调节因子，而与它在控制 T 细胞反应中的功能无关。
