The Role of Cystatin F in Regulating Neuroinflammation and Demyelination in Spinal Cord Poliovirus Infection

Background Knowledge

Cystatin F is a secreted lysosomal cysteine protease inhibitor associated with every stage of virus-related neurological diseases, including host defense, demyelination, and myelination. However, research on how Cystatin F affects the severity of neuropathology after central nervous system (CNS) viral infection is still insufficient.

Literature Source

A study published by Syage et al. in the Journal of Neuroinflammation in 2024 explored the role of Cystatin F in antiviral immune responses, demyelination, and myelin regeneration.

Research Objectives and Methods

The study used Cystatin F knockout mice (cst7-/-) infected with the neurotropic strain of mouse hepatitis virus (JHMV) to evaluate the role of Cystatin F in host defense, demyelination, and myelin regeneration. Methods such as fluorescent live cell staining, flow cytometry, and single-cell RNA sequencing (scRNA-seq) were used to identify immune cell infiltration and activation in the CNS, assess the degree of spinal cord demyelination, and evaluate myelin regeneration through electron microscopy and G-ratio calculations.

Research Results

Cystatin F-deficient mice were able to control viral replication in the CNS, but compared to control mice, they showed increased T cell infiltration in the CNS, associated with more severe myelin and axonal damage and reduced myelin regeneration capacity. scRNA-seq results showed that Cystatin F-deficient mice had increased expression of transcripts encoding T cell chemokines CXCL9 and CXCL10, suggesting that Cystatin F may influence neuroinflammation and neuropathology by regulating the expression of these genes.

Research Conclusions

Cystatin F is not essential for mediating immune responses to JHMV replication in the CNS, but Cystatin F-deficient mice exhibited more severe clinical disease after infection, associated with exacerbated demyelination and impaired myelin regeneration. These findings support that Cystatin F can influence pro-inflammatory gene expression, T cell activation, or glial cell responses.

Research Significance and Value

This study emphasizes the important role of Cystatin F in regulating neuroinflammation and demyelination, especially after viral infection. Given the potential role of Cystatin F in regulating immune responses, this provides new research directions and therapeutic targets for treating neurological diseases.

Keywords: Cystatin F, Coronavirus, Microglia, Demyelination, Myelin regeneration