| First Author | Ashby KM | Year | 2024 |
| Journal | Sci Immunol | Volume | 9 |
| Issue | 97 | Pages | eadp1139 |
| PubMed ID | 39058762 | Mgi Jnum | J:359208 |
| Mgi Id | MGI:7782820 | Doi | 10.1126/sciimmunol.adp1139 |
| Citation | Ashby KM, et al. (2024) Sterile production of interferons in the thymus affects T cell repertoire selection. Sci Immunol 9(97):eadp1139 |
| abstractText | 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. |
