The circulating microRNome demonstrates distinct lymphocyte subset-dependent signatures

Upon activation, lymphocytes release vesicles containing microRNAs (miRNAs). However, little is known as to whether this release results in modulation of circulating miRNAs (the miRNome) in the serum. The present work aims to identify lymphocyte subset-specific signatures of miRNAs within the serum circulating miRNome. We therefore assessed serum miRNA expression profiles in wild-type mice; in mice lacking either CD4(+) T cells, CD8(+) T cells, invariant natural killer T (iNKT) cells, or B cells; and, as a control, in mice in which Dicer has been ablated in T lymphocytes. We found that specific serum miRNAs are differentially modulated when different lymphocyte subsets are lacking. In particular, the serum level of miR-181b-5p, previously demonstrated to be fundamental for the development of iNKT cells, is specifically reduced in mice in which iNKT cells are absent. Interestingly, our results indicate a direct link between the biological role of a single miRNA in lymphocyte development and its serum level, and prove that even a population composed of relatively few cells in vivo, such as iNKT lymphocytes, has a measurable effect on the serum circulating miRNome.