IRF-1 deficiency skews the differentiation of dendritic cells toward plasmacytoid and tolerogenic features
IRF-1 deficiency skews the differentiation of dendritic cells toward plasmacytoid and tolerogenic features
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DOI：
10.1189/jlb.0406246
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发表时间：
2006-12-01
影响因子：
5.5
通讯作者：
Battistini, A.
中科院分区：
文献类型：
--
作者：
Gabriele, L.;Fragale, A.;Battistini, A.
IFN调节因子（IRFs）家族的成员是在免疫系统的稳态和功能中发挥重要作用的转录调节因子。最近的研究表明，该家族的一些成员直接参与树突状细胞（DC）不同亚群的发育。在这里，我们报告说，IRF-1是一个强大的调制器的发展和功能成熟的DC。IRF-1缺陷小鼠（IRF-1（-/-））表现出浆细胞样DC占优势，常规DC选择性减少，尤其是CD 8 α（+）亚群。IRF-1（-/-）脾DC产生促炎细胞因子（如IL-12）的能力明显受损。相反，它们表达高水平的IL-10、TGF-β和致耐受酶吲哚胺2，3双加氧酶。因此，IRF-1（-/-）DC在离体和体内病毒感染后不能完全成熟并保留浆细胞样和致耐受性特征。因此，来自IRF-1（-/-）nice的DC在刺激同种异体T细胞增殖方面效率较低，而是在同种异体CD 4（+）CD 25（+）调节性T细胞中诱导IL-10介导的抑制活性。总之，这些结果表明，IRF-1是DC分化和成熟的关键调节因子，对这些细胞的功能活化和致耐受性潜力发挥多种作用。
Members of the IFN regulatory factors (IRFs) family are transcriptional regulators that play essential roles in the homeostasis and function of the immune system. Recent studies indicate a direct involvement of some members of the family in the development of different subsets of dendritic cells (DC). Here, we report that IRF-1 is a potent modulator of the development and functional maturation of DC. IRF-1-deficient mice (IRF-1(-/-)) exhibited a predominance of plasmacytoid DC and a selective reduction of conventional DC, especially the CD8 alpha(+) subset. IRF-1(-/-) splenic DC were markedly impaired in their ability to produce proinflammatory cytokines such as IL-12. By contrast, they expressed high levels of IL-10, TGF-beta, and the tolerogenic enzyme indoleamine 2,3 dioxygenase. As a consequence, IRF-1(-/-) DC were unable to undergo full maturation and retained plasmacytoid and tolerogenic characteristics following virus infection ex vivo and in vivo. Accordingly, DC from IRF-1(-/-) njice were less efficient in stimulating the proliferation of allogeneic T cells and instead, induced an IL-10-mediated, suppressive activity in allogeneic CD4(+)CD25(+) regulatory T cells. Together, these results indicate that IRF-1 is a key regulator of DC differentiation and maturation, exerting a variety of effects on the functional activation and tolerogenic potential of these cells.