CD1d依賴的脂質(zhì)代謝重塑在巨噬細(xì)胞中調(diào)節(jié)先天免疫反應(yīng)

中文摘要：

細(xì)胞代謝的變化支撐著巨噬細(xì)胞的激活，但目前對(duì)關(guān)鍵免疫分子如何調(diào)節(jié)巨噬細(xì)胞的代謝程序知之甚少。在這里，我們揭示了抗原呈遞分子CD1d在脂質(zhì)代謝控制中的作用。我們展示了缺乏CD1d的巨噬細(xì)胞表現(xiàn)出代謝重編程，脂質(zhì)代謝途徑下調(diào)，外源性脂質(zhì)進(jìn)口增加。這種代謝重組為巨噬細(xì)胞增強(qiáng)對(duì)先天信號(hào)的反應(yīng)做好了準(zhǔn)備，因?yàn)镃D1d缺失的細(xì)胞在刺激類 Toll 樣受體后表現(xiàn)出更高的信號(hào)傳導(dǎo)和細(xì)胞因子分泌。在機(jī)制上，CD1d通過控制脂質(zhì)轉(zhuǎn)運(yùn)蛋白CD36的內(nèi)吞作用來調(diào)節(jié)脂質(zhì)進(jìn)口，而阻斷通過CD36的脂質(zhì)攝取可以恢復(fù)巨噬細(xì)胞的代謝和免疫反應(yīng)。因此，我們的數(shù)據(jù)揭示了CD1d作為巨噬細(xì)胞中一個(gè)炎癥-代謝回路的關(guān)鍵調(diào)節(jié)因子，這一功能獨(dú)立于其對(duì)T細(xì)胞反應(yīng)的調(diào)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.

論文信息：

論文題目：CD1d-dependent rewiring of lipid metabolism in macrophages regulates innate immune responses

期刊名稱：Nature Communications

時(shí)間期卷：13, Article number: 6723 (2022)

在線時(shí)間：2022年11月7日

DOI：doi.org/10.1038/s41467-022-34532-x

產(chǎn)品信息：

貨號(hào)：CP-005-005

規(guī)格：5ml+5ml

品牌：Liposoma

產(chǎn)地：荷蘭

名稱：Clodronate Liposomes and Control Liposomes

辦事處：Target Technology(靶點(diǎn)科技)

氯膦酸鹽二鈉脂質(zhì)體清除單核巨噬細(xì)胞，在LPS誘導(dǎo)的炎性模型中單核巨噬細(xì)胞功能研究，荷蘭Liposoma巨噬細(xì)胞清除劑Clodronate Liposomes見刊于Nature Communications：CD1d依賴的脂質(zhì)代謝重塑在巨噬細(xì)胞中調(diào)節(jié)先天免疫反應(yīng)。

Liposoma巨噬細(xì)胞清除劑Clodronate Liposomes氯膦酸二鈉脂質(zhì)體的材料和方法：

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.

材料和方法文獻(xiàn)截圖：