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芳香烃受体在咪喹莫特诱导的银屑病小鼠模型中调节产生白细胞介素-22的细胞增殖/募集。

AhR modulates the IL-22-producing cell proliferation/recruitment in imiquimod-induced psoriasis mouse model.

作者信息

Cochez Perrine M, Michiels Camille, Hendrickx Emilie, Van Belle Astrid B, Lemaire Muriel M, Dauguet Nicolas, Warnier Guy, de Heusch Magali, Togbe Dieudonnée, Ryffel Bernhard, Coulie Pierre G, Renauld Jean-Christophe, Dumoutier Laure

机构信息

Ludwig Institute for Cancer Research, Brussels Branch, Belgium.

de Duve Institute, Université catholique de Louvain, Brussels, Belgium.

出版信息

Eur J Immunol. 2016 Jun;46(6):1449-59. doi: 10.1002/eji.201546070.

Abstract

IL-22 has a detrimental role in skin inflammatory processes, for example in psoriasis. As transcription factor, AhR controls the IL-22 production by several cell types (i.e. Th17 cells). Here, we analyzed the role of Ahr in IL-22 production by immune cells in the inflamed skin, using an imiquimod-induced psoriasis mouse model. Our results indicate that IL-22 is expressed in the ear of imiquimod-treated Ahr(-/-) mice but less than in wild-type mice. We then studied the role of AhR on three cell populations known to produce IL-22 in the skin: γδ T cells, Th17 cells, and ILC3, and a novel IL-22-producing cell type identified in this setting: CD4(-) CD8(-) TCRβ(+) T cells. We showed that AhR is required for IL-22 production by Th17, but not by the three other cell types, in the imiquimod-treated ears. Moreover, AhR has a role in the recruitment of γδ T cells, ILC3, and CD4(-) CD8(-) TCRβ(+) T cells into the inflamed skin or in their local proliferation. Taken together, AhR has a direct role in IL-22 production by Th17 cells in the mouse ear skin, but not by γδ T cells, CD4(-) CD8(-) TCRβ(+) T cells and ILCs.

摘要

白细胞介素-22(IL-22)在皮肤炎症过程中具有有害作用,例如在银屑病中。作为转录因子,芳烃受体(AhR)控制多种细胞类型(即辅助性T细胞17型[Th17细胞])产生IL-22。在此,我们使用咪喹莫特诱导的银屑病小鼠模型,分析了AhR在炎症皮肤中免疫细胞产生IL-22过程中的作用。我们的结果表明,在咪喹莫特处理的AhR基因敲除(Ahr(-/-))小鼠耳部表达了IL-22,但表达量低于野生型小鼠。然后,我们研究了AhR对已知在皮肤中产生IL-22的三种细胞群体的作用:γδT细胞、Th17细胞和3型固有淋巴细胞(ILC3),以及在此背景下鉴定出的一种新的产生IL-22的细胞类型:CD4(-)CD8(-)T细胞受体β(TCRβ)(+)T细胞。我们发现,在咪喹莫特处理的耳部,Th17细胞产生IL-22需要AhR,但其他三种细胞类型则不需要。此外,AhR在将γδT细胞、ILC3和CD4(-)CD8(-)TCRβ(+)T细胞募集到炎症皮肤中或其局部增殖过程中发挥作用。综上所述,AhR在小鼠耳部皮肤中对Th17细胞产生IL-22具有直接作用,但对γδT细胞、CD4(-)CD8(-)TCRβ(+)T细胞和固有淋巴细胞(ILC)则没有直接作用。

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