| 摘要: | 細胞內脂肪小滴的生成是維持生理恆定的重要機制，其過度堆積與病理性代謝紊亂息息相關，例如肥胖、糖尿病、癌症以及粥狀動脈硬化等。脂肪小滴的代謝已被證實對於維持先天性和適應性免疫十分重要，然而它在周邊免疫細胞中所扮演之角色仍有待釐清。本篇研究利用多色流式細胞儀搭配螢光探針，發現健康人周邊血液中樹突狀細胞 (CD3-CD19-CD56-CD11+)、單核球細胞 (CD3-CD19-CD56-CD14+)、自然殺手細胞 (CD3-CD19-CD56+) 和 B 細胞 (CD3-CD19+) 含有較多脂滴。 此外，常見的脂質清道夫受體CD36，也在脂滴堆積的樹突狀細胞和單核球細胞中高表達。利用體外血脂異常實驗模型，以氧化態脂蛋白 (oxLDL) 短時間刺激周邊單核細胞後發現脂滴大量堆積於CD14+單核球細胞，但並沒有改變主要免疫細胞群的表現。 特別的是，oxLDL 刺激誘導樹突狀細胞、單核細胞以及B細胞後則進一步誘導CD36的高表達。然而，oxLDL刺激後脂滴堆積的CD14+單核細胞顯示出對oxLDL的胞內攝取異常，即使其高表達CD36受體，表明脂質清除已存在缺陷。 最後，我們證實oxLDL體外刺激引起單核細胞朝向第一型極化現象，並伴隨著細胞內脂滴積累和CD36表達的增加。本研究描述了一種監測周邊血液免疫細胞中脂滴生成和CD36表達的方法，並證實單核球細胞的第一型極化現象來自於oxLDL對單核細胞的可能免疫調節作用。
Lipid droplets (LDs) are intracellular organelles that store energy, which is essential for maintaining physiological homeostasis. Excessive LDs are related to pathological metabolic disorders. LDs metabolism is necessary for maintaining innate and adaptive immunity; however, its significance in peripheral immune cells is still unclear. In this study, measurement of intracellular LDs contents by using flow cytometry-based immune profiling showed a significant original generation of LDs in dendritic cells (DCs, CD3-CD19-CD56-CD11c+), monocytes (CD3-CD19-CD56-CD14+), natural killer cells (NK, CD3-CD19-CD56+), and B cells (CD3-CD19+). At the same time, CD36, the primary scavenger receptor for lipids, was also substantially expressed in LD-accumulated DCs and monocytes. Ex-vivo short-term stimulation with oxidized LDL (oxLDL) to imitate an experimental dyslipidemia model showed a considerable increase in the formation of LDs in CD14+ monocytes, but there were no alternations in the immune cell populations. Additionally, CD36 expression was also upregulated in LD-susceptible cells after oxLDL treatment. Notably, even though CD36 expression was upregulated following oxLDL pre-stimulation, CD14+ monocytes displayed a blockage in the uptake of extra Dil-oxLDL, indicating a failure in lipid clearance. Finally, we found that exogenous treatment of oxLDL caused monocyte polarizing to type 1 phenotype, accompanied by upregulation of LDs accumulation and CD36 expression. Overall, this study developed a method to detect LDs generation and CD36 expression in peripheral immune cells and revealed an immunomodulatory effect on monocytes by inducing them to polarize toward the type 1 phenotype under oxLDL stimulation. |
