MCAM+CD161− Th17 Subset Expressing CD83 Enhances Tc17 Response in Psoriasis

C-C趋化因子受体6型 细胞毒性T细胞 CD8型 白细胞介素17 免疫学 FOXP3型 细胞生物学 免疫系统 白细胞介素21 化学 生物 体外 趋化因子 趋化因子受体 生物化学
作者
Kohei Maeda,Toshihiro Tanioka,Rei Takahashi,Hideaki Watanabe,Hirohiko Sueki,Masafumi Takimoto,Shinichi Hashimoto,Kazuho Ikeo,Yusuke Miwa,Tsuyoshi Kasama,Sanju Iwamoto
出处
期刊:Journal of Immunology [American Association of Immunologists]
卷期号:210 (12): 1867-1881 被引量:2
标识
DOI:10.4049/jimmunol.2200530
摘要

Recent studies have highlighted the pathogenic roles of IL-17-producing CD8+ T cells (T-cytotoxic 17 [Tc17]) in psoriasis. However, the underlying mechanisms of Tc17 induction remain unclear. In this study, we focused on the pathogenic subsets of Th17 and their mechanism of promotion of Tc17 responses. We determined that the pathogenic Th17-enriched fraction expressed melanoma cell adhesion molecule (MCAM) and CCR6, but not CD161, because this subset produced IL-17A abundantly and the presence of these cells in the peripheral blood of patients has been correlated with the severity of psoriasis. Intriguingly, the serial analysis of gene expression revealed that CCR6+MCAM+CD161-CD4+ T cells displayed the gene profile for adaptive immune responses, including CD83, which is an activator for CD8+ T cells. Coculture assay with or without intercellular contact between CD4+ and CD8+ T cells showed that CCR6+MCAM+CD161-CD4+ T cells induced the proliferation of CD8+ T cells in a CD83-dependent manner. However, the production of IL-17A by CD8+ T cells required exogenous IL-17A, suggesting that intercellular contact via CD83 and the production of IL-17A from activated CD4+ T cells elicit Tc17 responses. Intriguingly, the CD83 expression was enhanced in the presence of IL-15, and CD83+ cells stimulated with IL-1β, IL-23, IL-15, and IL-15Rα did not express FOXP3. Furthermore, CCR6+MCAM+CD161-CD4+ T cells expressing CD83 were increased in the peripheral blood of patients, and the CD83+ Th17-type cells accumulated in the lesional skin of psoriasis. In conclusion, pathogenic MCAM+CD161- Th17 cells may be involved in the Tc17 responses via IL-17A and CD83 in psoriasis.
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