ADP-ribosylation factor-like 8b 是系统性红斑狼疮小鼠模型发育所必需的。
ADP-ribosylation factor-like 8b is required for the development of mouse models of systemic lupus erythematosus.
机构信息
Division of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Minatoku, Tokyo, Japan.
Department of Biochemistry, Meiji Pharmaceutical University, Kiyose, Tokyo, Japan.
出版信息
Int Immunol. 2019 Mar 28;31(4):225-237. doi: 10.1093/intimm/dxy084.
Toll-like receptor 7 (TLR7) and type I interferons (IFN-1) are essential for the development of systemic lupus erythematosus (SLE) models such as BXSB.Yaa and 2,6,10,14-tetramethyl-pentadecane (TMPD)-induced experimental lupus. However, the mechanism underlying the development of SLE remains undefined. We report a requirement for ADP-ribosylation factor-like 8b (Arl8b) for TLR7-dependent IFN-1 production in plasmacytoid dendritic cells (pDCs). We analyzed whether Arl8b plays a role in two SLE models by comparing wild-type and Arl8b-deficient Arl8b GeneTrap (Arl8bGt/Gt) mice. We found that BXSB.Yaa Arl8bGt/Gt mice showed none of the abnormalities characterized in BXSB.Yaa mice. TMPD treatment of Arl8bGt/Gt mice significantly inhibited the development of SLE. pDCs were required for TMPD-induced peritonitis. Our data demonstrate that Arl8b contributes to disease pathogenesis in two SLE models via IFN-1-dependent and -independent mechanisms and suggest that Arl8b is an attractive new target for therapeutic intervention in SLE.
Toll 样受体 7（TLR7）和 I 型干扰素（IFN-1）对于系统性红斑狼疮（SLE）模型的发展至关重要，如 BXSB.Yaa 和 2,6,10,14-四甲基十五烷（TMPD）诱导的实验性狼疮。然而，SLE 发展的机制仍未确定。我们报告了 ADP-核糖基化因子样 8b（Arl8b）在浆细胞样树突状细胞（pDC）中 TLR7 依赖性 IFN-1 产生中的作用。我们通过比较野生型和 Arl8b 基因敲除（Arl8bGt/Gt） Arl8b 基因陷阱（Arl8bGt/Gt）小鼠，分析了 Arl8b 是否在两种 SLE 模型中发挥作用。我们发现，BXSB.Yaa Arl8bGt/Gt 小鼠没有 BXSB.Yaa 小鼠的任何异常特征。TMPD 处理 Arl8bGt/Gt 小鼠显著抑制 SLE 的发展。pDC 是 TMPD 诱导的腹膜炎所必需的。我们的数据表明，Arl8b 通过 IFN-1 依赖性和非依赖性机制促进两种 SLE 模型的发病机制，并表明 Arl8b 是 SLE 治疗干预的一个有吸引力的新靶点。
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