Fatty acid‐binding protein 5 limits the generation of Foxp3+ regulatory T cells through regulating plasmacytoid dendritic cell function in the tumor microenvironment
Fatty acid‐binding protein 5 limits the generation of Foxp3+ regulatory T cells through regulating plasmacytoid dendritic cell function in the tumor microenvironment
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DOI：
10.1002/ijc.33777
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发表时间：
2021-08
影响因子：
6.4
通讯作者：
Shuhei Kobayashi;Tunyanat Wannakul;Kaname Sekino;Yu Takahashi;Yoshiteru Kagawa;Hirofumi Miyazaki;Banlanjo Umaru;Shuhan Yang;Yui Yamamoto;Y. Owada
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文献类型：
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作者：
Shuhei Kobayashi;Tunyanat Wannakul;Kaname Sekino;Yu Takahashi;Yoshiteru Kagawa;Hirofumi Miyazaki;Banlanjo Umaru;Shuhan Yang;Yui Yamamoto;Y. Owada
浆细胞样树突状细胞(PDC)通过产生大量的I型干扰素来促进病毒的清除。最近的研究表明，pDC调节多种炎症性疾病的发病机制，如癌症。脂肪酸结合蛋白5(FABP5)是一种诱导生物反应的长链脂肪酸的细胞伴侣。虽然FABP介导的脂质代谢在各种免疫细胞中的作用已经得到了很好的研究，但它在pDC中的作用仍然不清楚。这项研究比较了野生型和Fabp5型−/−小鼠，首次提供了证据表明，FABP5介导的脂代谢调节pDC在肿瘤微环境中对炎症和耐受基因表达模式的承诺，以及对Toll样受体刺激的响应。此外，我们还证明了pDC中FABP5的缺乏会影响周围的细胞环境，并且pDC中FABP5的表达支持适当的调节性T细胞(Tregs)的产生。综上所述，我们的研究结果表明，PDC FABP5通过控制脂质代谢，发挥着肿瘤免疫的重要调节作用。
Plasmacytoid dendritic cells (pDCs) promote viral elimination by producing large amounts of Type I interferon. Recent studies have shown that pDCs regulate the pathogenesis of diverse inflammatory diseases, such as cancer. Fatty acid‐binding protein 5 (FABP5) is a cellular chaperone of long‐chain fatty acids that induce biological responses. Although the effects of FABP‐mediated lipid metabolism are well studied in various immune cells, its role in pDCs remains unclear. This study, which compares wild‐type and Fabp5−/− mice, provides the first evidence that FABP5‐mediated lipid metabolism regulates the commitment of pDCs to inflammatory vs tolerogenic gene expression patterns in the tumor microenvironment and in response to toll‐like receptor stimulation. Additionally, we demonstrated that FABP5 deficiency in pDCs affects the surrounding cellular environment, and that FABP5 expression in pDCs supports the appropriate generation of regulatory T cells (Tregs). Collectively, our findings reveal that pDC FABP5 acts as an important regulator of tumor immunity by controlling lipid metabolism.