Division of Immunology, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4, Sakamoto, Nagasaki, 852-8523 Japan.
Division of Molecular and Cellular Immunoscience, Department of Biomolecular Sciences, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan; Department of Immunology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima, 890-8544 Japan.
Immunity. 2016 Mar 15;44(3):672-682. doi: 10.1016/j.immuni.2016.02.011. Epub 2016 Mar 8.
Interleukin-27 (IL-27) is a heterodimeric regulatory cytokine of the IL-12 family, which is produced by macrophages, dendritic cells, and B cells upon stimulation through innate immune receptors. Here, we described regulatory CD4(+) T cells that produce IL-27 in response to T cell receptor stimulation during malaria infection, inhibiting IL-2 production and clonal expansion of other T cells in an IL-27-dependent manner. IL-27-producing CD4(+) T cells were Foxp3(-)CD11a(+)CD49d(+) malaria antigen-specific CD4(+) T cells and were distinct from interferon-γ (IFN-γ) producing Th1 or IL-10 producing Tr1 cells. In mice lacking IL-27 in T cells, IL-2 production was restored and clonal expansion and IFN-γ production by specific CD4(+) T cells were improved, culminating in reduced parasite burden. This study highlights a unique population of IL-27 producing regulatory CD4(+) T cells and their critical role in the regulation of the protective immune response against malaria parasites.
白细胞介素-27（IL-27）是一种白细胞介素-12 家族的异二聚体调节细胞因子，由巨噬细胞、树突状细胞和 B 细胞在先天免疫受体受到刺激时产生。在这里，我们描述了在疟疾感染期间，调节性 CD4(+) T 细胞在 T 细胞受体刺激下产生 IL-27，以 IL-27 依赖的方式抑制其他 T 细胞的 IL-2 产生和克隆扩增。产生 IL-27 的 CD4(+) T 细胞是 Foxp3(-)CD11a(+)CD49d(+)疟疾抗原特异性 CD4(+) T 细胞，与产生干扰素-γ (IFN-γ)的 Th1 或产生 IL-10 的 Tr1 细胞不同。在缺乏 T 细胞中 IL-27 的小鼠中，IL-2 的产生得到恢复，特异性 CD4(+) T 细胞的克隆扩增和 IFN-γ 的产生得到改善，最终寄生虫负荷减少。这项研究强调了一种独特的产生 IL-27 的调节性 CD4(+) T 细胞群体及其在调节针对疟疾寄生虫的保护性免疫反应中的关键作用。
