Department of Pediatrics, University Clinic Carl Gustav Carus, TU Dresden, Dresden, Germany.
Institute of Immunology, Medical Faculty TU Dresden, Dresden, Germany.
Clin Immunol. 2020 Jul;216:108466. doi: 10.1016/j.clim.2020.108466. Epub 2020 May 27.
STING-associated vasculopathy with onset in infancy (SAVI) is an autoimmune disease caused by heterozygous gain of function mutations of STING (stimulator of interferon genes) that had initially been classified as a type I interferonopathy. We recently reported a genetically engineered mouse strain carrying a common SAVI-associated STING mutation. These STING N153S/WT mice reproduce key features of SAVI, including lung inflammation, loss of T cells in spleen and blood, splenomegaly and thymic hypoplasia. Here we show that αβ T lymphocytopenia is due to disrupted T cell development and is associated with impaired T cell activation and a relative increase in γδ T cell numbers. These alterations were not rescued by additional knockout of the type I IFN receptor (IFNAR1). Collectively, our findings consolidate the concept that constitutive STING signalling leads to a SCID-like phenotype in STING N153S/WT mice.
婴儿期起病的 STING 相关性血管病（SAVI）是一种由 STING（干扰素基因刺激物）的杂合获得性功能突变引起的自身免疫性疾病，最初被归类为 I 型干扰素病。我们最近报道了一种携带常见 SAVI 相关 STING 突变的基因工程小鼠品系。这些 STING N153S/WT 小鼠再现了 SAVI 的关键特征，包括肺部炎症、脾脏和血液中 T 细胞缺失、脾肿大和胸腺发育不良。在这里，我们表明 αβ T 淋巴细胞减少是由于 T 细胞发育紊乱引起的，与 T 细胞活化受损和 γδ T 细胞数量相对增加有关。这些改变不能通过额外敲除 I 型 IFN 受体（IFNAR1）来挽救。总之，我们的研究结果证实了这样一种概念，即组成性 STING 信号导致 STING N153S/WT 小鼠出现 SCID 样表型。
