Single-cell RNA sequencing of cerebrospinal fluid reveals the expansion of innate lymphoid cells with upregulated transposable elements in multiple sclerosis

Abstract

Background: Multiple sclerosis (MS) is a chronic and often immune-mediated demyelinating disease with no absolute treatment. Transposable elements (TEs) are getting more attention as a possible culprit in neurodegenerative disease. However, to the best of our knowledge, there is no study to examine the possible association of TE expression and its potential role in MS pathogenesis at the single-cell level. Result: In this study, we reanalyzed single-cell RNA sequencing data of human cerebrospinal fluid (CSF) samples. Our result revealed that TEs are overexpressed in a cluster, annotated as innate lymphoid cells (ILCs). Moreover, the enrichment analysis of the associated transcription factors (TFs) with highly upregulated TEs in ILCs revealed the relevance of the TFs with immune pathways and cis-regulatory regions in DNA. Conclusions: We propose that upregulated TEs in ILCs are in accordance with the plasticity of ILCs as TEs could insert themselves in coding or regulatory regions of immune-related genes, and represent themselves as immune-related TF binding sites. We also hypothesize that presenting the TE-derived antigens by ILCs with overexpressed TEs could re-activate T cell-mediated immunity in the CNS of MS patients. So this study could indicate a possible mechanism that is mediated by TEs in ILC plasticity and their possible role in MS pathogenicity. Also, we suggest that repurposing the nucleoside reverse transcriptase inhibitors (NRTIs) or developing new high-efficacy NRTIs would be a feasible approach in MS treatment.