Restoration of CD56dim NK Cells by Methotrexate Contributes to the Treatment of Juvenile Idiopathic Arthritis

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in childhood. To elucidate the mechanism of methotrexate (MTX) treatment-induced JIA clinical remission, we conducted single-cell RNA sequencing (scRNA-seq) analysis of peripheral blood mononuclear cells (PBMCs) obtained from a female JIA patient before and after MTX treatment. Besides, we integrated our data with public bulk RNA-seq data. We found that the proportion of the CD56dim NK subsets was restored after MTX treatment, suggesting that CD56dim NK subsets are mainly involved in MTX treatment-induced JIA clinical remission. Differential expression analysis showed that the NK cell-mediated cytotoxicity pathway was riched in CD56dim NK subsets. Furthermore, bulk RNA-seq results showed that MTX-treated NK-92 cell lines were also enriched for NK cell-mediated cytotoxicity pathways. Our data highlight the importance of CD56dim NK subsets in MTX treatment-induced JIA clinical remission. Overall design: We conducted single-cell RNA sequencing (scRNA-seq) analysis of peripheral blood mononuclear cells (PBMCs) obtained from a female JIA patient before and after MTX treatment. Besides, we conducted bulk RNA-seq of NK-92 cell lines with or without MTX treatment for further validation. *************************************************************** Submitter states that missing raw files are due to patient privacy concerns. ***************************************************************