Unidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells
نویسندگان
چکیده
The immune synapse is an exquisitely evolved means of communication between T cells and antigen-presenting cells (APCs) during antigen recognition. Recent evidence points to the transfer of RNA via exosomes as a novel mode of intercellular communication. Here we show that exosomes of T, B and dendritic immune cells contain microRNA (miRNA) repertoires that differ from those of their parent cells. We investigate whether miRNAs are exchanged during cognate immune interactions, and demonstrate the existence of antigen-driven unidirectional transfer of miRNAs from the T cell to the APC, mediated by the delivery of CD63+ exosomes on immune synapse formation. Inhibition of exosome production by targeting neutral sphingomyelinase-2 impairs transfer of miRNAs to APCs. Moreover, miRNAs transferred during immune synapsis are able to modulate gene expression in recipient cells. Thus, our results support a mechanism of cellular communication involving antigen-dependent, unidirectional intercellular transfer of miRNAs by exosomes during immune synapsis.
منابع مشابه
Exosome-loaded Paclitaxel: Preparation and toxicity evaluation on two glioblastoma cell lines
Objective(s): Exosomes are endogenous nanovesicles act as intercellular communication tools which have been considered to utilize as drug delivery systems. As transporting therapeutic molecules into brain has obstacles, preparing exosomes which have the potential to pass through its barriers is great challenge. Methods: Exosomes isolated from cell culture media of U87 glioblastoma ...
متن کاملExosomal cancer immunotherapy is independent of MHC molecules on exosomes
Peptide-loaded exosomes are promising cancer treatment vehicles; however, moderate T cell responses in human clinical trials indicate a need to further understand exosome-induced immunity. We previously demonstrated that antigen-loaded exosomes carry whole protein antigens and require B cells for inducing antigen-specific T cells. Therefore, we investigated the relative importance of exosomal m...
متن کاملThe role of exosomes contents on genetic and epigenetic alterations of recipient cancer cells
Exosomes, as a mediator of cell-to-cell transfer of genetic information, act an important role in intercommunication between tumor cells and their niche including fibroblasts, endothelial cells, adipocytes and monocytes. Several studies have shown that tumor cells can influence their neighboring cells by releasing exosomes. These exosomes provide signaling cues for stimulation, activation, prol...
متن کاملAntigen Presentation by MHC-Dressed Cells
Professional antigen-presenting cells (APCs) such as conventional dendritic cells (DCs) process protein antigens to MHC-bound peptides and then present the peptide-MHC complexes to T cells. In addition to this canonical antigen presentation pathway, recent studies have revealed that DCs and non-APCs can acquire MHC class I (MHCI) and/or MHC class II (MHCII) from neighboring cells through a proc...
متن کاملExosomes bearing HLA-DR1 molecules need dendritic cells to efficiently stimulate specific T cells.
Exosomes are small vesicles (60-100 nm) secreted by various cell types upon the fusion of endosomal compartments with the plasma membrane. Exosomes from antigen-presenting cells (APC), such as B lymphocytes and dendritic cells (DC), bear MHC class II molecules. In addition, the injection of DC-derived exosomes was reported to elicit potent T cell responses in vivo. Here, we analyzed the activat...
متن کامل