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

Area of Science:

• Neuroimmunology
• Molecular Biology

Background:

• Stimulator of interferon genes (STING) is a key sensor in innate immunity, activating type I interferon (IFN) signaling crucial for neuroinflammation.
• The precise role of STING in the pathogenesis of multiple sclerosis (MS) and its specific impact on central nervous system (CNS) lesion development remain incompletely understood.

Purpose of the Study:

• To investigate the role of STING in the development of localized CNS lesions within a focal experimental autoimmune encephalomyelitis (EAE) model, specifically targeting the corpus callosum.
• To compare lesion induction and characteristics in wild-type and STING-deficient mice to elucidate STING's contribution to neuroinflammation and demyelination.

Main Methods:

• A focal EAE model was induced in wild-type and STING-deficient (STING^gt/gt) mice.
• Lesion analysis involved immunohistochemistry, flow cytometry, and transcriptomic profiling.
• Immune cell infiltration and gene expression, particularly interferon-stimulated genes (ISGs), were quantified.

Main Results:

• STING-deficient mice exhibited significantly larger demyelinated lesions compared to wild-type controls.
• Reduced expression of interferon-stimulated genes (ISGs) was observed in STING-deficient mice.
• Distinct alterations in immune cell infiltration patterns were identified in the absence of STING.

Conclusions:

• STING signaling plays a protective role by limiting the severity of demyelinated lesions in focal EAE.
• STING promotes essential IFN responses and regulates immune cell infiltration, thereby mitigating neuroinflammatory damage.
• These findings highlight STING as a potential therapeutic target for managing MS and related neuroinflammatory conditions.