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

## TL;DR

This study shows that Aire helps control interferon signaling in the thymus, which is important for immune cell development and preventing autoimmune reactions in mice.

## Contribution

The study reveals Aire's role in regulating type I interferon signaling in thymic immune cells and epithelial cells.

## Key findings

- Aire deficiency reduces type I interferon-stimulated genes in late thymocytes and thymic epithelial cells.
- Interferon signaling in bone marrow immune cells is not affected by Aire deficiency.
- Aire influences thymic interferon production and immune cell transcriptomes.

## Abstract

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.

Single cell RNA sequencing reveals reduced expression of type I interferon-stimulated genes in late stage thymocytes and thymic epithelial cells when Aire is deficient, suggesting a role for Aire in thymic interferon production.