Macrophages overexpressing Aire induce CD4+Foxp3+ T cells
Macrophages overexpressing Aire induce CD4+Foxp3+ T cells
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巨噬细胞过表达 Aire 诱导 CD4 Foxp3 T 细胞
DOI：
10.3892/mmr.2012.1150
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发表时间：
2013-01-01
影响因子：
3.4
通讯作者：
Yang, Wei
中科院分区：
文献类型：
--
作者：
Sun, Jitong;Fu, Haiying;Yang, Wei
Aire通过调节数千个基因的转录在中枢免疫耐受中起重要作用。然而，Aire在外周免疫系统中的作用知之甚少。调节性T（Treg）细胞被认为是维持外周耐受性所必需的，但Aire对外周免疫系统中Treg细胞的影响目前尚不清楚。在本研究中，我们通过将过表达Aire的RAW 264. 7细胞或其上清液与脾细胞共培养来研究过表达Aire的巨噬细胞对CD 4（+）Foxp 3（+）Treg细胞的影响。结果表明，过表达Aire的巨噬细胞通过细胞-细胞接触或共培养上清液增强了Foxp 3 mRNA的表达，并诱导了脾细胞中Treg细胞的不同亚群。TGF-β是在细胞上清液共培养后观察到的CD 4（+）CD 45 RA（+）Foxp 3（hi）T细胞和活化Treg（aTreg）水平增加中的关键分子。Treg细胞的亚群由Aire过表达的巨噬细胞诱导，并且通过靶向Aire来操纵Treg细胞可能提供用于治疗炎性或自身免疫性疾病的方法。
Aire plays an important role in central immune tolerance by regulating the transcription of thousands of genes. However, the role of Aire in the peripheral immune system is poorly understood. Regulatory T (Treg) cells are considered essential for the maintenance of peripheral tolerance, but the effect of Aire on Treg cells in the peripheral immune system is currently unknown. In this study, we investigated the effects of macrophages overexpressing Aire on CD4(+)Foxp3(+) Treg cells by co-culturing Aire-overexpressing RAW264.7 cells or their supernatant with splenocytes. The results show that macrophages overexpressing Aire enhanced the expression of Foxp3 mRNA and induced different subsets of Treg cells in splenocytes through cell-cell contact or a co-culture supernatants. TGF-beta is a key molecule in the increases of CD4(+)CD45RA(+)Foxp3(hi) T cell and activating Treg (aTreg) levels observed following cell-supernatant co-culturing. Subsets of Treg cells were induced by Aire-overexpressing macrophages, and the manipulation of Treg cells by the targeting of Aire may provide a method for the treatment of inflammatory or autoimmune diseases.