# STING Signaling Deficiency Exacerbates Demyelination and Immune Infiltration in Focal EAE Lesions

## TL;DR

This study shows that a lack of STING signaling worsens brain lesions and immune responses in a mouse model of multiple sclerosis.

## Contribution

The novel finding is that STING signaling limits lesion severity in focal EAE by promoting IFN responses and regulating immune infiltration.

## Key findings

- STING-deficient mice had significantly larger demyelinated lesions compared to wild-type mice.
- STING deficiency was associated with reduced interferon-stimulated gene (ISG) expression and altered immune cell infiltration.

## Abstract

Stimulator of interferon genes (STING) is a cytosolic DNA sensor that activates type I interferon (IFN) signaling, which plays a key role in neuroinflammation. Although the role of STING in experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS), remains debated, its involvement in the development of CNS lesions, particularly within localized pathology, modeled here by targeting the corpus callosum, has yet to be explored. Using a focal EAE model, we compared the induction of lesions in wild-type and STING-deficient (STINGgt/gt) mice. Lesions were analyzed by immunohistochemistry, flow cytometry, and transcriptomics. STING-deficient mice had significantly larger demyelinated lesions, reduced ISG expression, and modified immune cell infiltration. STING signaling limits lesion severity in focal EAE by promoting IFN responses and regulating immune infiltration. These findings position STING as a potential target for MS therapy.