MicroRNA profiling of thymocytes undergoing stress-induced atrophy (86.10)

Abstract

Abstract Acute thymic atrophy occurs in a number of clinical situations including pregnancy, irradiation, immunosuppressive therapy, and bacterial infections. Lipopolysaccharide (LPS), a component of Gram-negative bacteria, can induce thymic atrophy within 48 hrs. While cytokines, corticosteroids, and TNF can mediate various aspects of thymic atrophy, little is known about the possible role of microRNAs. MicroRNAs (miRNAs) are a class of non-coding, small RNAs that regulate gene expression in many biological systems including the immune system. To assess whether miRNAs might regulate LPS-induced thymic atrophy, we performed miRNA profiling. C57BL/6 mice were injected with LPS and RNA was extracted from the thymus at various time points post-injection. LPS induced an overall decrease in thymic cellularity within 72 hours, with a significant decrease in the CD4/CD8 double positive population (p=<0.05). Preliminary microarray analysis yielded 8 and 6 unique miRNAs that were up- and down-regulated, respectively. We are currently confirming the microarray data with Northern blots probing for selected miRNAs. MiRNA expression patterns unique to different diseases or disorders are crucial to not only elucidating the role of miRNAs in the innate and adaptive immune response, but also in developing novel therapeutic treatments.