T-cell and B-cell Immunology
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It was 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, highlighting the importance of sterile thymic IFN production in generating a self-tolerant TCR repertoire.
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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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@article{Ashby2024Sterile,
title = {Sterile production of interferons in the thymus affects T cell repertoire selection},
author = {K. Maude Ashby and Matouš Vobořil and Oscar Camilo Salgado and S. Thera Lee and Ryan J. Martinez and Christine H. O’Connor and Elise R. Breed and Shuya Xuan and Charles R. Roll and Saumith Bachigari and Hattie Heiland and Daniel B. Stetson and Sergei V. Kotenko and Kristin A. Hogquist},
journal = {Science Immunology},
year = {2024},
doi = {10.1126/sciimmunol.adp1139},
url = {https://doi.org/10.1126/sciimmunol.adp1139}
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