Lee Wonyong, Kim Hyeong Su, Baek Song Yi, Lee Gap Ryol
Department of Life Science, Sogang University, 35 Baekbeom-ro, Mapo-gu, Seoul, 121-742, Korea
Cell Mol Immunol. 2016 Nov;13(6):785-794. doi: 10.1038/cmi.2015.72. Epub 2015 Jul 13.
Recent studies have suggested that regulatory T (Treg) cells comprise a heterogeneous population that regulates various aspects of the immune response, and that Treg cells use the factors that are expressed in their target cells to regulate them. We searched for factors that regulate Th1 response in Treg cells using a meta-analysis. In the process, we discovered that transcription factor interferon regulatory factor 8 (IRF8) was selectively expressed in Treg and Th1 cells. IRF8-deficient Treg cells showed defective expression of CXCR3 and aberrant expression of the Il4 and Il17 genes. Upon treatment with alpha galactosyl-C18-ceramide (αGal-C18-Cer), IRF8-deficient mice showed defective Treg cell recruitment in the liver. Eliciting Th1 immune response by anti-CD40 antibody injection in mice induced IRF8 expression in Treg cells. The expression of IRF8 was induced by Foxp3 in Treg cells. IRF8 had no effect on T-bet expression in Treg and vice versa. Thus, our results strongly suggest that IRF8 controls Th1 immune response in Treg cells independent of T-bet.
最近的研究表明,调节性T(Treg)细胞构成了一个异质性群体,可调节免疫反应的各个方面,并且Treg细胞利用其靶细胞中表达的因子来调节这些细胞。我们使用荟萃分析寻找调节Treg细胞中Th1反应的因子。在此过程中,我们发现转录因子干扰素调节因子8(IRF8)在Treg和Th1细胞中选择性表达。IRF8缺陷型Treg细胞显示CXCR3表达缺陷以及Il4和Il17基因表达异常。用α-半乳糖基-C18-神经酰胺(αGal-C18-Cer)处理后,IRF8缺陷型小鼠在肝脏中显示出Treg细胞募集缺陷。通过在小鼠中注射抗CD40抗体引发Th1免疫反应可诱导Treg细胞中IRF8的表达。IRF8在Treg细胞中由Foxp3诱导表达。IRF8对Treg细胞中T-bet的表达没有影响,反之亦然。因此,我们的结果强烈表明,IRF8独立于T-bet控制Treg细胞中的Th1免疫反应。