Exosome-delivered microRNAs of “chromosome 19 microRNA cluster” as immunomodulators in pregnancy and tumorigenesis

We have advanced the hypothesis that as part of the feto-maternal communication miRNAs of C19MC serve immunomodulatory functions in the placenta and confer a growth advantage to thyroid nodules by protecting them against autoimmune attacks. More precisely, the exosomes containing these miRNAs may specifically target immune cells in their local environment as well as systemically by transferring their cargo to recipient cells. Within these target cells the transferred miRNAs can interact with mRNAs of the recipient cells thereby suppressing their immune-specific functions.Experiments used to demonstrate the immunomodulatory capacity of placenta-derived exosomes can be modified by transfecting the target cells with those miRNAs of C19MC represented in placental exosomes.Mimics of C19MC-derived miRNAs might develop to useful drug candidates for the treatment of autoimmune disease as e.g. rheumatoid arthritis and Sj？gren’s syndrome and for the prevention of transplant rejection. In case of tumor entities with elevated expression of C19MC miRNAs these miRNAs may be interesting targets for treatment with appropriate antagonists.First being described in 1989 [1], structural rearrangements of chromosomal band 19q13 are a frequent non-random cytogenetic abnormality in thyroid adenomas and adenomatous goiters. By applying molecular-cytogenetic methods on established cell lines it was possible to narrow down the breakpoints to a region of about 150 kbp [2] which was later shown to harbor C19MC (chromosome 19 microRNA cluster), the largest human microRNA cluster at all [3] (Figure 1). As a rule, by the chromosomal rearrangements the microRNAs of this cluster and the neighboring miR-371-3 cluster become strongly upregulated [4]. Of these both clusters C19MC is remarkable not only because of its sheer size encoding more than 50 mature microRNAs but also because of its “young” age. The whole cluster is primate-specific [3] and thus must have evolved within a relatively short time