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Expression of leukotriene B 4 receptor 1 defines functionally distinct DCs that control allergic skin inflammation
Cellular & Molecular Immunology ( IF 21.8 ) Pub Date : 2020-10-09 , DOI: 10.1038/s41423-020-00559-7
Tomoaki Koga 1, 2 , Fumiyuki Sasaki 1, 3 , Kazuko Saeki 1 , Soken Tsuchiya 4 , Toshiaki Okuno 1 , Mai Ohba 1 , Takako Ichiki 1 , Satoshi Iwamoto 1 , Hirotsugu Uzawa 1 , Keiko Kitajima 5 , Chikara Meno 5 , Eri Nakamura 6 , Norihiro Tada 6 , Yoshinori Fukui 7 , Junichi Kikuta 8 , Masaru Ishii 8 , Yukihiko Sugimoto 4 , Mitsuyoshi Nakao 2 , Takehiko Yokomizo 1
Affiliation  

Leukotriene B4 (LTB4) receptor 1 (BLT1) is a chemotactic G protein-coupled receptor expressed by leukocytes, such as granulocytes, macrophages, and activated T cells. Although there is growing evidence that BLT1 plays crucial roles in immune responses, its role in dendritic cells remains largely unknown. Here, we identified novel DC subsets defined by the expression of BLT1, namely, BLT1hi and BLT1lo DCs. We also found that BLT1hi and BLT1lo DCs differentially migrated toward LTB4 and CCL21, a lymph node-homing chemoattractant, respectively. By generating LTB4-producing enzyme LTA4H knockout mice and CD11c promoter-driven Cre recombinase-expressing BLT1 conditional knockout (BLT1 cKO) mice, we showed that the migration of BLT1hi DCs exacerbated allergic contact dermatitis. Comprehensive transcriptome analysis revealed that BLT1hi DCs preferentially induced Th1 differentiation by upregulating IL-12p35 expression, whereas BLT1lo DCs accelerated T cell proliferation by producing IL-2. Collectively, the data reveal an unexpected role for BLT1 as a novel DC subset marker and provide novel insights into the role of the LTB4-BLT1 axis in the spatiotemporal regulation of distinct DC subsets.



中文翻译:


白三烯 B 4 受体 1 的表达定义了控制过敏性皮肤炎症的功能不同的 DC



白三烯 B 4 (LTB 4 ) 受体 1 (BLT1) 是一种趋化 G 蛋白偶联受体,由白细胞(例如粒细胞、巨噬细胞和活化的 T 细胞)表达。尽管越来越多的证据表明 BLT1 在免疫反应中发挥着至关重要的作用,但它在树突状细胞中的作用仍然很大程度上未知。在这里,我们鉴定了由 BLT1 表达定义的新 DC 子集,即 BLT1 hi和 BLT1 lo DC。我们还发现 BLT1 hi和 BLT1 lo DC 分别差异性地向 LTB 4和 CCL21(一种淋巴结归巢化学引诱剂)迁移。通过生成LTB 4产生酶LTA 4 H 敲除小鼠和CD11c启动子驱动的Cre重组酶表达BLT1条件敲除(BLT1 cKO)小鼠,我们发现BLT1 hi DC的迁移加剧了过敏性接触性皮炎。综合转录组分析显示,BLT1 hi DC 通过上调 IL-12p35 表达优先诱导 Th1 分化,而 BLT1 lo DC 通过产生 IL-2 加速 T 细胞增殖。总的来说,这些数据揭示了 BLT1 作为新型 DC 子集标记物的意想不到的作用,并为 LTB 4 -BLT1 轴在不同 DC 子集的时空调节中的作用提供了新的见解。

更新日期:2020-10-11
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