Characterization of mouse serum exosomal small RNA content: The origins and their roles in modulating inflammatory response

In the last decade, although studies on exosomal microRNAs (miRNAs) derived from serum and other body fluids have increased dramatically; the contents and biological significance of serum exosomes under normal conditions remain unclear. In the present study, we profiled the small RNA content of mouse serum exosomes (mSEs) using small RNAseq and found that fragments of transfer RNAs (tRNAs) and miRNAs were the two predominant exosomal RNA species, accounting for approximately 60% and 10% of mapped reads, respectively. Moreover, 466 known and 5 novel miRNAs were identified from two independent experiments, among which the five most abundant miRNAs (miR-486a-5p, miR-22-3p, miR-16-5p, miR-10b-5p and miR-27b-3p) accounted for approximately 60% of all the aligned miRNA sequences. As inferred from the identities of the well known cell- or tissue-specific miRNAs, mSEs were primarily released by RBCs, liver and intestinal cells. Bioinformatics analysis revealed over half of the top 20 miRNAs by abundance were involved in inflammatory responses and further in vitro experiments demonstrated that mSEs potently primed macrophages towards the M2 phenotype. To the best of our knowledge, this is the first study to profile small RNAs from mSEs. In addition to providing a reference for future biomarker studies and extrapolating their origins, our data also suggest the roles of mSEs in maintaining internal homeostasis under normal conditions.