胸腺中干扰素的无菌产生会影响 T 细胞的选择。

IF 17.6 1区 医学 Q1 IMMUNOLOGY
K. Maude Ashby, Matouš Vobořil, Oscar C. Salgado, S. Thera Lee, Ryan J. Martinez, Christine H. O’Connor, Elise R. Breed, Shuya Xuan, Charles R. Roll, Saumith Bachigari, Hattie Heiland, Daniel B. Stetson, Sergei V. Kotenko, Kristin A. Hogquist
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引用次数: 0

摘要

Ⅰ型和Ⅲ型干扰素(IFNs)在感染过程中会被强烈诱导,并保护细胞免受病毒感染。I 型和 III 型 IFNs 也会在胸腺中以低水平稳态产生;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,我们发现极少数 AIRE+ 小鼠胸腺上皮细胞可持续产生 I 型和 III 型 IFNs,不受微生物刺激的影响。抗原递呈细胞对胸腺 IFN 具有高度反应性,胸腺 1 型常规树突状细胞、巨噬细胞和 B 细胞的活化和成熟都需要 IFN。IFN感应的缺失会导致调节性T细胞选择减少、T细胞受体(TCR)库多样性降低以及对外周IFN信号传导过程中表达的自身抗原的自反应性T细胞反应增强。因此,在胸腺中持续暴露于 IFNs 是产生耐受性和多样性 TCR 复合物的必要条件。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Sterile production of interferons in the thymus affects T cell repertoire selection
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.
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来源期刊
Science Immunology
Science Immunology Immunology and Microbiology-Immunology
CiteScore
32.90
自引率
2.00%
发文量
183
期刊介绍: Science Immunology is a peer-reviewed journal that publishes original research articles in the field of immunology. The journal encourages the submission of research findings from all areas of immunology, including studies on innate and adaptive immunity, immune cell development and differentiation, immunogenomics, systems immunology, structural immunology, antigen presentation, immunometabolism, and mucosal immunology. Additionally, the journal covers research on immune contributions to health and disease, such as host defense, inflammation, cancer immunology, autoimmunity, allergy, transplantation, and immunodeficiency. Science Immunology maintains the same high-quality standard as other journals in the Science family and aims to facilitate understanding of the immune system by showcasing innovative advances in immunology research from all organisms and model systems, including humans.
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