Resolvin E1 inhibits dendritic cell migration in the skin and attenuates contact hypersensitivity responses.
Resolvin E1 inhibits dendritic cell migration in the skin and attenuates contact hypersensitivity responses.
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DOI：
10.1084/jem.20150381
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发表时间：
2015-10-19
期刊：
影响因子：
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通讯作者：
Kabashima K
中科院分区：
文献类型：
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作者：
Sawada Y;Honda T;Hanakawa S;Nakamizo S;Murata T;Ueharaguchi-Tanada Y;Ono S;Amano W;Nakajima S;Egawa G;Tanizaki H;Otsuka A;Kitoh A;Dainichi T;Ogawa N;Kobayashi Y;Yokomizo T;Arita M;Nakamura M;Miyachi Y;Kabashima K
Sawada等人。报道称，Resolvin E1(RvE1)在稳态和炎症条件下均下调皮肤DC的运动，并在接触性超敏反应中发挥抗炎作用。他们提出，LTB4-BLT1信号阻断可能是RvE1发挥调节作用的主要机制。ω-3多不饱和脂肪酸是一种脂类介体，可在多种小鼠模型中发挥有效的抗炎作用。RvE1在获得性免疫反应中的抗炎机制被归因于抑制树突状细胞(DC)产生细胞因子。在这项研究中，我们用双光子显微镜在接触性超敏(CHS)模型中研究了RvE1对DC运动的影响，发现RvE1损害了皮肤中的DC运动。此外，RvE1还减弱了引流淋巴结中T细胞的启动和皮肤中效应性T细胞的激活，从而减轻了CHS的皮肤炎症。相反，白三烯B4(LTB4)诱导DC肌动蛋白细丝重组，并通过BLT1激活CDC42和rac1而增加DC的运动能力，而BLT1可被RvE1取消。总之，我们的结果表明，RvE1通过抑制皮肤DC的运动而减弱皮肤获得性免疫反应，这可能是通过阻断LTB4-BLT1信号来实现的。
Sawada et al. report that Resolvin E1 (RvE1) down-regulates DC motility in both steady state and inflammatory conditions in the skin and exerts its antiinflammatory effects in contact hypersensitivity. They propose the LTB4-BLT1 signaling blockade as a possible major mechanism through which RvE1 exerts its regulatory effects. Resolvin E1 (RvE1) is a lipid mediator derived from ω3 polyunsaturated fatty acids that exerts potent antiinflammatory roles in several murine models. The antiinflammatory mechanism of RvE1 in acquired immune responses has been attributed to attenuation of cytokine production by dendritic cells (DCs). In this study, we newly investigated the effect of RvE1 on DC motility using two-photon microscopy in a contact hypersensitivity (CHS) model and found that RvE1 impaired DC motility in the skin. In addition, RvE1 attenuated T cell priming in the draining lymph nodes and effector T cell activation in the skin, which led to the reduced skin inflammation in CHS. In contrast, leukotriene B4 (LTB4) induced actin filament reorganization in DCs and increased DC motility by activating Cdc42 and Rac1 via BLT1, which was abrogated by RvE1. Collectively, our results suggest that RvE1 attenuates cutaneous acquired immune responses by inhibiting cutaneous DC motility, possibly through LTB4-BLT1 signaling blockade.