MicroRNAs modulate chemokine expression in naive CD8 T cells (44.19)

Abstract Chemokines play a pivotal role in regulating T cell function and migration in a space- and time-tight fashion. With aging, the levels of several chemokines alter in serum and have detrimental impact on the immune function. However, the mechanisms that regulate chemokine expressions and their age-associated alteration are not fully understood. MicroRNAs (miRNA) are key regulators for gene expression at the posttranscriptional level but their roles in the age-associated change of gene expression in T cells have not been examined. We sought to understand the role of miRNA in regulation of chemokine expression in CD8 T cells by profiling chemokines and miRNAs in naïve and memory CD8 T cells. Six miRNAs (miR-99a, -125b, -186, -335, -424, and -542-5p) were highly expressed in naïve CD8 T cells. In addition, we found that miR-125b, -335, and -186 have a putative binding site in the 3’ UTR of CC chemokine ligand 4 (CCL4), CCL5, and CXC chemokine ligand 5 (CXCL5), respectively. These chemokines are highly expressed in activated T cells and increased serum levels with age. Currently, we are testing these individual miRNA in the chemokine-reporter transfected Jurkat cells and in human primary CD8 T cells from young (≤ 30 yrs) and old (≥ 70yrs) donors. Our preliminary findings suggest that miRNA regulates chemokine expression in CD8 T cells and such regulation may change with age.