Transcription factor MafB-mediated inhibition of type I interferons in plasmacytoid dendritic cells
Transcription factor MafB-mediated inhibition of type I interferons in plasmacytoid dendritic cells
复制标题
浆细胞样树突状细胞中转录因子 MafB 介导的 I 型干扰素抑制
DOI：
10.1093/intimm/dxab103
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发表时间：
2022
影响因子：
4.4
通讯作者：
Katsuaki Hoshino
中科院分区：
文献类型：
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作者：
Hiroyuki Saiga;Masaki Ueno;Takashi Tanaka;Tsuneyasu Kaisho;Katsuaki Hoshino
I型干扰素（IFN-α和IFN-β）是由活化的浆细胞样树突状细胞（pDC）分泌的免疫调节细胞因子，参与机体对病原性感染的天然防御和自身免疫性疾病寻常型银屑病的发病机制。先前的研究已经表明，E26转化特异性（Ets）家族转录因子Spi-B可以与IFN调节因子（IRF）-7协同反式激活I型IFN启动子，并且是pDC中I型IFN产生所需的。然而，pDC对I型IFN负调控的机制仍不清楚。在这项研究中，我们报告了一个碱性亮氨酸拉链（bZip）转录因子v-maf肌肉腱膜纤维肉瘤癌基因同源物B（Maf B）抑制诱导的I型干扰素在pDCs。MafB的高表达以剂量依赖的方式抑制I型IFN基因的反式激活。在分子水平上，MafB与Spi-B的Ets结构域相互作用并干扰IRF-7-Spi-B复合。MafB mRNA表达的降低和MafB蛋白在免疫反应早期的降解导致pDC中I型IFN的增强。体内研究表明MafB参与抵抗咪喹莫特诱导的银屑病样皮肤炎症。总之，这些发现表明MafB作为pDC中I型IFN诱导的负调节剂，并且在维持免疫稳态中起重要作用。
Type I IFNs (IFN-α and IFN-β), immunomodulatory cytokines secreted from activated plasmacytoid dendritic cells (pDCs), contribute to the innate defense against pathogenic infections and the pathogenesis of the autoimmune disease psoriasis vulgaris. A previous study has shown that an E26 transformation-specific (Ets) family transcription factor Spi-B can transactivate the type I IFN promoter in synergy with IFN regulatory factor (IRF)-7 and is required for type I IFN production in pDCs. However, the mechanism of negative regulation of type I IFNs by pDCs remains unknown. In this study, we report that a basic leucine zipper (bZip) transcription factor v-maf musculoaponeurotic fibrosarcoma oncogene homolog B (MafB) suppresses the induction of type I IFNs in pDCs. The elevated expression of MafB inhibited the transactivation of type I IFN genes in a dose-dependent manner. At the molecular level, MafB interacted with the Ets domain of Spi-B and interfered with IRF-7–Spi-B complexation. Decreased MafB mRNA expression and degradation of MafB protein in the early phase of immune responses led to the enhancement of type I IFNs in pDCs.In vivostudies indicated that MafB is involved in resistance against imiquimod-induced psoriasis-like skin inflammation. Overall, these findings demonstrate that MafB acts as a negative regulator of type I IFN induction in pDCs and plays an important role in maintaining immune homeostasis.