Aire-dependent interferon signalling shapes thymocyte maturation and central tolerance in mice

Autoimmune regulator (Aire) orchestrates the presentation of self-antigens to developing thymocytes, playing a key role in central tolerance. However, it remains unclear how Aire deficiency influences immune cell development and function. Recent studies show that Aire-expressing thymic epithelial cells produce type I and III interferons, but how impaired IFN signalling from Aire deficiency contributes to immune dysregulation remains unclear. Single-cell RNA sequencing was used to profile immune cells from Aire-deficient and wild-type mice across thymus, bone marrow, and lymph nodes. In the thymus, thymocytes at late maturation stages, non-conventional T cells, myeloid cells, immature Ccl21+ mTECs and cTECs had reduced expression of type I interferon-stimulated genes in the absence of Aire. In contrast, interferon-stimulated gene expression in bone marrow immune cells appeared independent of Aire. These findings support a role for Aire in thymic interferon production and highlight type I IFNs’ influence on transcriptomes of developing immune cells.