Type I and III interferons (IFNs) are robustly induced during infections and protect cells against viral infection. Both type I and III IFNs are also produced at low levels in the thymus at steady state; however, their role in T cell development and immune tolerance is unclear. Here, we found that both type I and III IFNs were constitutively produced by a very small number of AIRE + murine thymic epithelial cells, independent of microbial stimulation. Antigen-presenting cells were highly responsive to thymic IFNs, and IFNs were required for the activation and maturation of thymic type 1 conventional dendritic cells, macrophages, and B cells. Loss of IFN sensing led to reduced regulatory T cell selection, reduced T cell receptor (TCR) repertoire diversity, and enhanced autoreactive T cell responses to self-antigens expressed during peripheral IFN signaling. Thus, constitutive exposure to IFNs in the thymus is required for generating a tolerant and diverse TCR repertoire.

中文翻译：

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胸腺中干扰素的无菌产生影响 T 细胞库的选择


I 型和 III 型干扰素 (IFN) 在感染过程中被强烈诱导，并保护细胞免受病毒感染。在稳定状态下，胸腺中也会产生低水平的 I 型和 III 型干扰素。然而，它们在 T 细胞发育和免疫耐受中的作用尚不清楚。在这里，我们发现 I 型和 III 型 IFN 都是由极少数 AIRE 组成型产生的。 +小鼠胸腺上皮细胞，独立于微生物刺激。抗原呈递细胞对胸腺 IFN 高度敏感，胸腺 1 型常规树突状细胞、巨噬细胞和 B 细胞的激活和成熟需要 IFN。 IFN 感应的丧失导致调节性 T 细胞选择减少、T 细胞受体 (TCR) 库多样性减少以及自身反应性 T 细胞对外周 IFN 信号转导过程中表达的自身抗原的反应增强。因此，胸腺中持续暴露于 IFN 是产生耐受且多样化的 TCR 库所必需的。