核IκB家族蛋白IκBNS在小鼠模型中影响实验性自身免疫性脑脊髓炎的易感性。

The nuclear IκB family protein IκBNS influences the susceptibility to experimental autoimmune encephalomyelitis in a murine model.

作者信息

Kobayashi Shuhei, Hara Akira, Isagawa Takayuki, Manabe Ichiro, Takeda Kiyoshi, MaruYama Takashi

机构信息

Laboratory of Cell Recognition and Response, Tohoku University, Miyagi, Japan.

Department of Pathology, Gifu University Graduate School of Medicine, Gifu, Japan.

出版信息

PLoS One. 2014 Oct 27;9(10):e110838. doi: 10.1371/journal.pone.0110838. eCollection 2014.

The nuclear IκB family protein IκBNS is expressed in T cells and plays an important role in Interferon (IFN)-γ and Interleukin (IL)-2 production. IκB-ζ, the most similar homolog of IκBNS, plays an important role in the generation of T helper (Th)17 cells in cooperation with RORγt, a master regulator of Th17 cells. Thus, IκB-ζ deficient mice are resistant to Th17-dependent experimental autoimmune encephalomyelitis (EAE). However, IκB-ζ deficient mice develop the autoimmune-like Sjögren syndrome with aging. Here we found that IκBNS-deficient (Nfkbid-/-) mice show resistance against developing Th17-dependent EAE. We found that Nfkbid-/- T cells have decreased expression of IL-17-related genes and RORγt in response to Transforming Growth Factor (TGF)-β1 and IL-6 stimulation. Thus, IκBNS plays a pivotal role in the generation of Th17 cells and in the control of Th17-dependent EAE.

核IκB家族蛋白IκBNS在T细胞中表达，在干扰素（IFN）-γ和白细胞介素（IL）-2的产生中发挥重要作用。IκB-ζ是与IκBNS最相似的同源物，与Th17细胞的主要调节因子RORγt协同作用，在辅助性T细胞（Th）17细胞的产生中发挥重要作用。因此，IκB-ζ缺陷小鼠对Th17细胞依赖的实验性自身免疫性脑脊髓炎（EAE）具有抗性。然而，IκB-ζ缺陷小鼠随着年龄增长会发展出自身免疫样干燥综合征。在此，我们发现IκBNS缺陷（Nfkbid-/-）小鼠对Th17细胞依赖的EAE发展具有抗性。我们发现，在转化生长因子（TGF）-β1和IL-6刺激下，Nfkbid-/- T细胞中IL-17相关基因和RORγt的表达降低。因此，IκBNS在Th17细胞的产生以及Th17细胞依赖的EAE的控制中起关键作用。