MicroRNAs mediate autoimmune disease pathology (137.3)

Experimental autoimmune encephalomyelitis (EAE), studied as a model for multiple sclerosis (MS), is mediated by autoreactive CD4+ T cells. MicroRNAs (miRNAs) are a class of small, noncoding RNAs that regulate gene expression posttranscriptionally. Aberrant expression of miRNAs has been implicated in various disease processes. Recent evidence indicates that miRNAs are central to immune function and play a role in T cell responsiveness to antigen stimulation. We hypothesized that certain miRNAs would be differentially expressed in mice with EAE, and that these miRNAs represent critical mediators of autoimmune disease pathology. We utilized microarray technology, followed by PCR verification, to evaluate miRNA expression level at varying times during the EAE disease course. RNA was obtained from the lymph nodes and spleen during the acute and effector phases of EAE, and compared to animals receiving adjuvant alone. We found that several miRNAs are up- or downregulated during EAE and expression is temporally distinct. These data indicate that miRNAs represent a critical component of EAE pathology, and may be useful therapeutic targets or biomarkers in MS and other autoimmune diseases. Supported by NIH grants T32 GM068412, NS 48316 and AI 064320.