Sterile production of interferons in the thymus affects T cell repertoire selection.
Sci Immunol
; 9(97): eadp1139, 2024 Jul 26.
Article
in En
| MEDLINE
| ID: mdl-39058762
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Thymus Gland
/
Interferons
/
Mice, Inbred C57BL
Limits:
Animals
Language:
En
Journal:
Sci Immunol
/
Sci. immunol
/
Science immunology
Year:
2024
Document type:
Article
Affiliation country:
Estados Unidos
Country of publication:
Estados Unidos