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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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K. Maude Ashby
Matouš Vobořil
Oscar Camilo Salgado
Science Immunology
University of Washington
Rutgers, The State University of New Jersey
University of Minnesota Medical Center
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Ashby et al. (Fri,) studied this question.
www.synapsesocial.com/papers/68e5ed5ab6db643587582853 — DOI: https://doi.org/10.1126/sciimmunol.adp1139
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