Immune activation associates with the intracellular generation of reactive oxygen species
(ROS). To elicit effective immune responses, ROS levels must be balanced. Emerging evidence
shows that ROS‐mediated signal transduction can be regulated by selenoproteins such as
methionine sulfoxide reductase B1 (MsrB1). However, how the selenoprotein shapes immunity
remains poorly understood. Here, we demonstrated that MsrB1 plays a crucial role in the ability of
dendritic cells (DCs) to provide the antigen presentation and costimulation that are needed for
cluster of differentiation antigen four (CD4) T‐cell priming in mice. We found that MsrB1 regulated
signal transducer and activator of transcription‐6 (STAT6) phosphorylation in DCs. Moreover, both
in vitro and in vivo, MsrB1 potentiated the lipopolysaccharide (LPS)‐induced Interleukin‐12 (IL‐12)
production by DCs and drove T‐helper 1 (Th1) differentiation after immunization. We propose that
MsrB1 activates the STAT6 pathway in DCs, thereby inducing the DC maturation and IL‐12
production that promotes Th1 differentiation. Additionally, we showed that MsrB1 promoted
follicular helper T‐cell (Tfh) differentiation when mice were immunized with sheep red blood cells.
This study unveils as yet unappreciated roles of the MsrB1 selenoprotein in the innate control of
adaptive immunity. Targeting MsrB1 may have therapeutic potential in terms of controlling
immune reactions.




中文翻译：

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硒蛋白MsrB1指导树突状细胞诱导T辅助1免疫反应。

免疫激活与细胞内活性氧
（ROS）的产生有关。为了引起有效的免疫反应，必须平衡ROS水平。新兴证据
表明，ROS介导的信号转导可以被诸如
蛋氨酸亚砜还原酶B1（MsrB1）的硒蛋白调控。然而，硒蛋白如何塑造免疫力
仍知之甚少。在这里，我们证明了MsrB1在
树突状细胞（DC）提供抗原呈递和共刺激的能力中起着至关重要的作用，而抗原呈递和共刺激是
小鼠分化抗原四（CD4）T细胞引发簇所必需的。我们发现MsrB1调节了DC中的
信号转导子和转录6（STAT6）磷酸化的活化剂。而且，两者
在体外和体内，MsrB1增强了
DC诱导的脂多糖（LPS）诱导的白介素12（IL-12）的产生，并在免疫后推动了T辅助1（Th1）的分化。我们建议
MsrB1激活DC中的STAT6途径，从而诱导DC成熟和
促进Th1分化的IL-12产生。此外，我们显示，
当小鼠用绵羊红细胞免疫时，MsrB1促进了卵泡辅助性T细胞（Tfh）的分化。
这项研究揭示了MsrB1硒蛋白在
适应性免疫的先天控制中尚未发挥的作用。就控制
免疫反应而言，靶向MsrB1可能具有治疗潜力。