| Description |
Immune cells need fine-tuned intercellular communication to properly respond to pathogens. Recently, researchers characterized a novel form of intercellular communication where microRNAs (miRNAs) can be transferred between cells in exosomes. Immune miRNAs, such as miR-155 and miR-146a, are important for posttranscriptional gene regulation and are essential for proper immune cell function. miR-155 is proinflammatory while miR-146a is an anti-inflammatory miRNA. We found that miR155 and miR-146a were released from bone marrow derived dendritic cells (BMDCs) within exosomes and are transferred to recipient BMDCs. Upon transfer, miRNAs decreased levels of their mRNA targets in recipient cells in a seed dependent manner and reprogrammed the cellular response to endotoxin. Exosomal miR-155 enhanced, whilemiR-146a reduced, inflammatory gene expression. Additionally, injection of miR146a containing exosomes into mice delivered miR-146a to various tissues and decreased inflammation in response to endotoxin, while miR-155 containing exosomes had the converse effect. Using the Rab27ab-/- (Rab27DKO) mice, which are deficient in producing exosomes, we assayed the importance of exosomes during endotoxin response in vivo and observed that these mice have defective response to endotoxin, which could be rescued with injection of WT exosomes. These results suggest that exosome uptake is important for proper response to endotoxin. We are continuing to utilize the Rab27DKO model t investigate the role of exosomes during normal hematopoietic development and during various disease states. We have found that Rab27DKO mice have a slight resting myeloproliferative disorder as well as over-activated T cells. Their extrameduallary hematopoiesis defects can be rescued by the presence of WT bone marrow (BM) and by injection of WT exosomes in resting mice suggesting that exosome uptake is important for; this phenotype. Additionally, in a multiple sclerosis (MS) model, Experimental Autoimmune Encephalomyelitis (EAE), Rab27DKO mice have worsened disease, which; we hypothesize is due to their increase in activated T cells at rest. Overall, our results suggest that exosomal communication is important for normal hematopoietic development and is involved in immune responses to challenge. |
