MICRORNA SPECIES REGULATE IMMUNE PROCESSES: A FOCUS ON NK CELLS IN CHRONIC ARTHRITIS

Abstract

Rheumatoid arthritis (RA) is a common chronic autoimmune/inflammatory disease involving innate/adaptive lymphocytes and soluble mediators. Natural killer (NK) cells are innate lymphocytes that direct immunity through cytotoxicity and cytokine production. The contributions of NK cells are ill-defined in RA, although their function(s) may be regulated by microRNAs (miRNAs). MiRNAs are non-coding RNAs that inhibit mRNA. To investigate the miRNA-NK cell interplay, we optimized highly efficient transfection techniques in serum-free media for enhancing or interrupting NK cell miRNA signaling. We targeted miRNAs that are expressed differently in patients with RA compared to healthy individuals. Our findings suggest that miR-146a-5p and miR-155-5p, two miRNAs upregulated in RA, reduce NKG2C expression, a hallmark of adaptive NK cells. We expect chronic overexpression of these miRNAs inhibits adaptive NK cells and their ability to eliminate auto-reactive B/T cells through antibody dependent cellular cytotoxicity (ADCC), thereby reducing treatment efficacy for therapies that rely on effective ADCC.