Decoding tRNA dynamics in neuroimmune disorders: From mechanistic insights to innovative therapies

The field of neuroimmunology is uncovering the profound impact of tRNA regulation on the pathophysiology of neuroimmune disorders such as multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). Current research illustrates that tRNA modifications—such as methylation by NSUN2 and production of tRNA-derived fragments—play crucial roles in modulating immune responses at neural-immune junctions. These modifications affect the translation of specific immune and neuroinflammatory proteins in T cells and glial cells. For instance, methylation of tRNA can facilitate the proper translation of IL-23R and GM-CSF, promoting neuroinflammation, while certain tRFs can paradoxically provide neuroprotection. Despite these insights, current treatments lack specificity in addressing the nuanced role of tRNA in disease processes. Emerging solutions, like CRISPR-mediated interventions and inhibitors of tRNA modification enzymes, promise refined approaches but require further exploration.

This Research Topic aims to elucidate cell-specific tRNA regulatory networks in neuroimmune dysregulation, focusing on how tRNA modifications and tRNA-derived fragments mediate interactions between CNS-resident glia and infiltrating lymphocytes. We seek to uncover the mechanistic basis of epitranscriptomic changes—such as m5C deposition in Th17 cells and stress-induced tRFs in astrocytes—that drive disease pathology. By integrating single-cell tRNAomics with experimental validations in preclinical models, we aim to pinpoint actionable targets for tRNA-directed therapies, such as biologics optimized for codon usage and small molecules targeting tRNA modifying enzymes, to enhance precision in neuroimmunology pharmacotherapies.

To gather further insights in the interplay between tRNA biology and neuroimmune disorders, we welcome articles addressing, but not limited to, the following themes:

- Modifications in tRNA landscapes in neuroimmune cells during inflammation and their functional roles.
- tRNA abundance shifts that influence the expression of immune checkpoint and myelin-related transcripts.
- Signaling pathways mediated by tRFs and their dualistic roles in inflammation and protection.
- Intersection of tRNA methylation changes with RNA editing mechanisms in disease progression.
- Applications of CRISPR technology for targeted modulation of pathogenic tRNA dynamics.

Submissions employing methodologies such as ribo-tRNA-seq or exploring translational and biomarker potential in clinical cohorts are highly encouraged. This Research Topic will consider original research, reviews, and emerging methodologies pertinent to advancing the understanding of tRNA regulation in neuroimmune contexts.