Ueyama Azumi, Imura Chihiro, Fusamae Yasuyuki, Tsujii Kenichiro, Furue Yoko, Aoki Miwa, Suzuki Minoru, Okuda Tomohiko, Oshima Itsuki, Yasui Kiyoshi, Shichijo Michitaka, Yamamoto Mina
Pharmaceutical Research Division, Shionogi & Co., Ltd., Toyonaka, Japan.
Pharmaceutical Research Division, Shionogi & Co., Ltd., Toyonaka, Japan.
J Dermatol Sci. 2017 Jan;85(1):27-35. doi: 10.1016/j.jdermsci.2016.10.007. Epub 2016 Oct 19.
Psoriasis is one of the most common immune-mediated chronic inflammatory skin disorders and is accompanied by erythematous scaly plaques. There is growing evidence that the IL-23/Th17 axis plays a critical role in development of the disease. It was recently shown that in addition to CD4 Th17 cells, various IL-17-producing cell subsets such as CD8 Tc17 cells, dermal γδ T cells, and innate lymphoid cells are also involved in the development of psoriatic inflammation in humans.
To investigate which subsets of IL-17-producing cells are involved in psoriasis-like skin inflammation in a TPA (tumor promoter 12-O-tetradecanoylphorbol-13-acetate)-induced K14.Stat3C mouse model.
Skin-infiltrating cells were isolated from inflamed lesions of TPA-treated K14.Stat3C transgenic mice, and analyzed for IL-17 producing cell subsets by flow cytometry.
We observed significantly increased numbers of IL-17-producing CD4 T cells, CD8 T cells and dermal γδ T cells in TPA-induced skin lesions of K14.Stat3C mice. Additionally, we found that another IL-17-producing T cell subset, αβ-TCR CD4CD8 double negative T cells (DN αβ T cells), was also increased in lesional skin. These IL-17-producing DN αβ T cells are NK1.1 negative, suggesting they are not natural killer T cells or mucosal associated invariant T cells. As well as other IL-17-producing cells, DN αβ T cells in the inflamed skin can also respond to IL-23 stimulation to produce IL-17. It is also suggested that DN αβ T cells may express retinoic acid-related orphan receptor gamma t and CC chemokine receptor 6.
In TPA-induced lesional skin of K14.Stat3C mice, IL-17-producing CD4 Th17 cells, CD8 Tc17 cells, dermal γδ T cells and TCR cells probably containing ILCs all participated in skin inflammation, which is similar to human clinical psoriatic features. Furthermore, we showed for the first time the possibility that an IL-17-producing DN αβ T cell subset is also involved in psoriatic inflammation.
银屑病是最常见的免疫介导的慢性炎症性皮肤病之一，伴有红斑鳞屑性斑块。越来越多的证据表明，白细胞介素-23/辅助性T细胞17（IL-23/Th17）轴在该疾病的发展中起关键作用。最近研究表明，除了CD4 Th17细胞外，各种产生白细胞介素-17（IL-17）的细胞亚群，如CD8 Tc17细胞、真皮γδ T细胞和固有淋巴细胞，也参与人类银屑病炎症的发展。
在佛波酯（TPA，12-O-十四酰佛波醇-13-乙酸酯）诱导的K14.Stat3C小鼠模型中，研究哪些产生IL-17的细胞亚群参与银屑病样皮肤炎症。
从经TPA处理的K14.Stat3C转基因小鼠的炎症病变中分离皮肤浸润细胞，通过流式细胞术分析产生IL-17的细胞亚群。
我们观察到在K14.Stat3C小鼠经TPA诱导的皮肤病变中，产生IL-17的CD4 T细胞、CD8 T细胞和真皮γδ T细胞数量显著增加。此外，我们发现另一个产生IL-17的T细胞亚群，αβ-TCR CD4CD8双阴性T细胞（DN αβ T细胞），在病变皮肤中也增加。这些产生IL-17的DN αβ T细胞NK1.1阴性，表明它们不是自然杀伤T细胞或黏膜相关恒定T细胞。与其他产生IL-17的细胞一样，炎症皮肤中的DN αβ T细胞也能对IL-23刺激作出反应以产生IL-17。还提示DN αβ T细胞可能表达维甲酸相关孤儿受体γt和CC趋化因子受体6。
在TPA诱导的K14.Stat3C小鼠病变皮肤中，产生IL-17的CD4 Th17细胞、CD8 Tc17细胞、真皮γδ T细胞以及可能包含固有淋巴细胞的TCR细胞均参与皮肤炎症，这与人类临床银屑病特征相似。此外，我们首次证明了产生IL-17的DN αβ T细胞亚群也参与银屑病炎症的可能性。
