Type I Interferon (IFN) signaling plays a critical role in dendritic cell (DC) development and functions. Inhibition of hyper type I IFN signaling promotes cDC2 subtype development. Relb is essential to development of cDC2 subtype and here we analyzed its effect on type I IFN signaling in DCs. We show that Relb suppresses the homeostatic type I IFN signaling in cDC2 cultures. TLR stimulation of FL-DCs led to RelB induction coinciding with fall in IFN signatures; conforming with the observation Relb expression reduced TLR stimulated IFN induction along with decrease in ISGs. Towards understanding mechanism, we show that effects of RelB are mediated by increased levels of IκBα. We demonstrate that RelB dampened antiviral responses by lowering ISG levels and the defect in cDC2 development in RelB null mice can be rescued in Ifnar1-/- background. Overall, we propose a novel role of RelB as a negative regulator of the type I IFN signaling pathway; fine tuning development of cDC2 subtype.

中文翻译：

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RelB抑制树突状细胞中的I型干扰素信号传导。

I型干扰素（IFN）信号传导在树突状细胞（DC）的发育和功能中起关键作用。抑制超I型IFN信号传导促进了cDC2亚型的发展。Relb对cDC2亚型的发育至关重要，在这里我们分析了其对DC中I型IFN信号传导的影响。我们表明Relb抑制cDC2文化中的稳态I型IFN信号传导。TLR刺激FL-DCs导致RelB诱导与IFN标记下降有关。与观察结果一致，Relb表达减少，TLR刺激IFN诱导，ISG减少。迈向了解机制，我们显示RelB的作用是由IκBα水平升高介导的。我们证明RelB通过降低ISG水平来减弱抗病毒反应，并且可以在Ifnar1-/-背景中挽救RelB null小鼠中cDC2发育中的缺陷。总的来说，我们提出了RelB作为I型IFN信号通路负调节剂的新作用。cDC2亚型的微调开发。