Department of Dermatology, Aarhus University Hospital, 8000 Aarhus, Denmark;
Department of Dermatology, Aarhus University Hospital, 8000 Aarhus, Denmark.
Immunohorizons. 2020 Nov 25;4(11):754-761. doi: 10.4049/immunohorizons.2000083.
IL-37 broadly suppresses inflammation in various disease models. However, studies of the regulation and role of IL-37 in psoriasis are limited and contradictive. Using transcriptome analysis, PCR, protein determination, and immunofluorescence, we demonstrated marked downregulation of IL-37 in biopsies from human lesional psoriasis skin compared with paired samples of nonlesional skin. Immunofluorescence analysis showed that IL-37 was localized to stratum granulosum of the epidermis. TNF-α stimulation of normal human epidermal keratinocytes led to increased expression through a p38 MAPK-mediated mechanism, whereas IL-17A, IL-17C, IL-17F, and IL-22 acted suppressively. Intradermal injection with recombinant human IL-37 into imiquimod-induced psoriasis skin of C57BL/6J mice demonstrated a trend toward a protective effect, however NS. Altogether, these results demonstrate that IL-37 is downregulated in human lesional psoriasis skin. This may be a consequence of the loss of stratum granulosum, but key cytokines in the development of psoriasis also seem to contribute to this downregulation.
IL-37 广泛抑制各种疾病模型中的炎症。然而，关于 IL-37 在银屑病中的调节和作用的研究有限且相互矛盾。通过转录组分析、PCR、蛋白测定和免疫荧光，我们证明与配对的非病变皮肤样本相比，人病变银屑病皮肤活检中 IL-37 的表达明显下调。免疫荧光分析显示，IL-37 定位于表皮颗粒层。TNF-α刺激正常人角质形成细胞通过 p38 MAPK 介导的机制导致其表达增加，而 IL-17A、IL-17C、IL-17F 和 IL-22 则起抑制作用。将重组人 IL-37 皮内注射到咪喹莫特诱导的 C57BL/6J 小鼠银屑病皮肤中显示出一种保护作用的趋势，然而无统计学意义。总之，这些结果表明，IL-37 在人病变银屑病皮肤中下调。这可能是颗粒层丧失的结果，但银屑病发展中的关键细胞因子似乎也促成了这种下调。
