Human Th17 Cells Express High Levels of Enzymatically Active Dipeptidylpeptidase IV (CD26)
Human Th17 Cells Express High Levels of Enzymatically Active Dipeptidylpeptidase IV (CD26)
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DOI：
10.4049/jimmunol.1103801
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发表时间：
2012-06-01
影响因子：
4.4
通讯作者：
Thimme, Robert
中科院分区：
文献类型：
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作者：
Bengsch, Bertram;Seigel, Bianca;Thimme, Robert
二肽基肽酶IV(CD26)是一种参与T细胞活化的多功能胞外酶，参与自身免疫的病理生理过程。由于产生IL-17的CD4(+)T细胞(Th17细胞)是自身免疫性疾病的重要介质，我们分析了CD26在人Th17细胞上的表达及其酶功能。CD26在不同的CD4(+)T辅助细胞亚群上的表达分析表明，与Th1、Th2和调节性T细胞相比，CD26在产生17型细胞因子(如IL-22、IL-17、GM-CSF或TNF)的CD4(+)T细胞上的表达最高。表型分析显示CD26(++)CD4(+)T细胞表达17类分化分子CD161、CCR6、IL-23R和维甲酸相关孤儿受体-γt。此外，分选的CD26(++)CD4(+)T细胞含有90-98%的Th17细胞，表明CD26(++)T细胞具有Th17血统。与CD161和CCR6的比较表明，CD26共表达的分析可能会改善Th17细胞的表型特征。值得注意的是，CD26(++)Th17细胞在肝炎和炎症性肠病患者的炎症组织中丰富。迁移实验中的功能分析表明，Th17细胞上表达的CD26具有酶活性。事实上，CD26负性调节趋化性CD4(+)T细胞对炎症趋化因子CXCL9-12的反应，而炎症趋化因子CXCL9-12可以通过药物阻断CD26的酶中心来恢复。综上所述，这些结果有力地表明，CD26可能有助于人类炎症性疾病中Th17细胞的免疫反应的协调。他们还建议，通过测定CD26的表达，可以方便地进行Th17细胞的表型分析。免疫学杂志，2012,188：5438-5447。
Dipeptidylpeptidase IV (CD26) is a multifunctional ectoenzyme involved in T cell activation that has been implicated in autoimmune pathophysiology. Because IL-17 producing CD4(+) T cells (Th17 cells) are important mediators of autoimmune disease, we analyzed the expression of CD26 and its enzymatic function on human Th17 cells. Analysis of CD26 expression on different CD4(+) T helper subsets showed that CD26 expression is highest on CD4(+) T cells producing type 17 cytokines (e.g., IL-22, IL-17, GM-CSF, or TNF) compared with Th1, Th2, and regulatory T cells. Phenotypic analysis revealed that CD26(++)CD4(+) T cells express the type 17 differentiation molecules CD161, CCR6, IL-23R, and retinoic acid-related orphan receptor-gamma t. Furthermore, sorted CD26(++)CD4(+) T cells contain >90-98% of Th17 cells, indicating that CD26(++) T cells harbor the Th17 lineage. A comparison with CD161 and CCR6 indicated that analysis of CD26 coexpression may improve the phenotypic characterization of Th17 cells. Of note, CD26(++) Th17 cells are enriched in the inflamed tissue of patients with hepatitis and inflammatory bowel disease. Functional analysis in migration assays revealed that CD26 expressed on Th17 cells is enzymatically active. Indeed, CD26 negatively regulates the chemotactic CD4(+) T cell response to the inflammatory chemokines CXCL9-12 that can be restored by pharmacological blockade of the enzymatic center of CD26. In summary, these results strongly suggest that CD26 may contribute to the orchestration of the immune response by Th17 cells in human inflammatory diseases. They also suggest that the phenotypic analysis of Th17 cells may be facilitated by determination of CD26 expression. The Journal of Immunology, 2012, 188: 5438-5447.