RNA-sequencing of CD۴+ T cells in Relapsing-Remitting Multiple Sclerosis patients at relapse; deciphering the involvement of novel genes and pathways

CD۴+ T cells known as a noteworthy potential modulator of inflammation in multiple sclerosis (MS). In thecurrent study, we investigated the transcriptome profile of CD۴+ T cells in relapsing-remitting MS (RRMS)patients at relapse phase. We performed RNA sequencing of CD۴+ T cells isolated from RRMS patients atrelapse phase and age- and sex-matched healthy controls. The edgeR statistical method was employed todetermine differential expression genes (DEGs). The gene set enrichment analysis was subsequentlyperformed. Applying physical interaction network, genes with higher degrees were selected as hub genes.A total of ۱۲۷۸ genes and ۱۰۳۴ gens were defined at significantly higher or lower levels, respectively, inCD۴+ T cells of RRMS patients at relapse phase as compared with healthy controls. The top up- and downregulatedgene were JAML and KDM۳A. The detected DEGs were remarkably on chromosomes ۱ and ۲,respectively. The DEGs were mainly enriched in pathways such as ‘regulation of transcription, DNAtemplated’,‘regulation of B cell receptor signaling pathway’, ‘protein phosphorylation’, ‘epidermal growthfactor receptor signaling pathway’, and ‘positive regulation of neurogenesis’. Moreover, ۱۶ KEGG pathwaysmostly associated with the immune system and viral infections were enriched. In the constructed physicalinteraction networks, UBA۵۲ and TP۵۳ were illustrated as the most highly ranked hub genes among up- anddown-regulated genes, correspondingly.Conclusions: By applying global transcriptome profiling of CD۴+ T cells, we deciphers the involvement ofseveral novel genes and pathways in MS pathogenesis. The present results need to be affirmed by in vivoand in vitro studies.

کلیدواژه ها:

RRMS ، CD۴+ T cells ، RNA-sequencing ، Transcriptome ، Functional modules ، Chromosomal enrichment