中文摘要：
细胞代谢的变化支撑着巨噬细胞的激活，但目前对关键免疫分子如何调节巨噬细胞的代谢程序知之甚少。在这里，我们揭示了抗原呈递分子CD1d在脂质代谢控制中的作用。我们展示了缺乏CD1d的巨噬细胞表现出代谢重编程，脂质代谢途径下调，外源性脂质进口增加。这种代谢重组为巨噬细胞增强对先天信号的反应做好了准备，因为CD1d缺失的细胞在刺激类 Toll 样受体后表现出更高的信号传导和细胞因子分泌。在机制上，CD1d通过控制脂质转运蛋白CD36的内吞作用来调节脂质进口，而阻断通过CD36的脂质摄取可以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作为巨噬细胞中一个炎症-代谢回路的关键调节因子，这一功能独立于其对T细胞反应的调控。
英文摘要：
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.
论文信息：
论文题目：CD1d-dependent rewiring of lipid metabolism in macrophages regulates innate immune responses
期刊名称：Nature Communications
时间期卷：13, Article number: 6723 (2022)
在线时间：2022年11月7日
DOI：doi.org/10.1038/s41467-022-34532-x
产品信息：
货号：CP-005-005
规格：5ml+5ml
品牌：Liposoma
产地：荷兰
名称：Clodronate Liposomes and Control Liposomes
办事处：Target Technology(靶点科技)
氯膦酸盐二钠脂质体清除单核巨噬细胞，在LPS诱导的炎性模型中单核巨噬细胞功能研究，荷兰Liposoma巨噬细胞清除剂Clodronate Liposomes见刊于Nature Communications：CD1d依赖的脂质代谢重塑在巨噬细胞中调节先天免疫反应。
Liposoma巨噬细胞清除剂Clodronate Liposomes氯膦酸二钠脂质体的材料和方法：
Generation of bone-marrow chimeras and in vivo models of disease
To generate bone-marrow chimeras, lethally irradiated recipient mice (CD45.1+CD45.2+) were adoptively transferred with bone marrow from WT (CD45.1+) and CD1d-KO (CD45.2+) donor mice mixed in a 50:50 ratio. Six weeks post transfer, pMacs were purified by cell sorting (with a FACSAria II; BD Biosciences) on the basis of congenic marker expression as CD11b+F4/80+CD45.1+ or CD11b+F4/80+CD45.2+ cells and used for further experiments.
For in vivo models of disease, WT mice were intraperitoneally (i.p.) injected with 200 μl of clodronate liposomes (Liposoma) and 3 days later were adoptively transferred with 3 × 106 WT or CD1d-KO BMDCs. Mice were injected i.p. with 40 mg/kg of SSO or vehicle control 4 h prior to LPS or E. coli injection. For induction of LPS-induced inflammation, mice were injected i.p. with 5 μg/g of LPS or vehicle control. Mice were bled via tail prick immediately prior to LPS injection and 4 h post injection. Temperature was measured using a rectal probe at the same time-points. For induction of peritonitis, mice were injected i.p. with 104 colony forming units (CFUs) of live E. coli (DH5α). Mice were bled via tail prick 18 h post E. coli injection and organs were collected and plated for CFU counts.
材料和方法文献截图：
