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
Ludwig Institute for Cancer Research, Brussels Branch, Belgium.
de Duve Institute, Université catholique de Louvain, Brussels, Belgium.
Eur J Immunol. 2016 Jun;46(6):1449-59. doi: 10.1002/eji.201546070.
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.
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。