Immature Dendritic Cell-Derived Exosomes: a Promise Subcellular Vaccine for Autoimmunity

Abstract

Exosomes, 60-90-nm-sized vesicles, are produced by a large number of cell types, including tumor cells, neurons, astrocytes, hemocytes, intestinal epithelial cells, and so on. Dendritic cell (DC), the most potent professional antigen-presenting cell in the immune system, produces exosomes in the course of maturation. Mature DCs produce exosomes with the ability to elicit potent immunoactivation, resulting in tumor eradication and bacterial or virus elimination. Given the notion that exosomes are stable and easy to be modified artificially, autologous mature DC-derived exosomes have been vaccinated into patients with malignant diseases. In clinical trials utilizing exosomes as therapeutic approaches, researchers observed considerable curative effect with little side effect. However, immature or suppressive DC-derived exosomes harbor anti-inflammatory properties distinct from mature DC-derived exosomes. In murine models of autoimmune disease and transplantation, immature DC-derived exosomes reduced T cell-dependent immunoactivation, relieved clinical manifestation of autoimmune disease, and prolonged survival time of transplantation. Although the exact mechanism of how immature DC-derived exosomes function in vivo is still unclear, and there are no clinical trials regarding application of exosome vaccine into patients with autoimmune disease, we will analyze the promise of immature DC-derived exosomes as a subcellular vaccine in autoimmunity in this review.

An update: Epstein-Barr virus and immune evasion via microRNA regulation

“…Exosomes are vesicles of 50-100 nm in size that are over-produced by most proliferating cell types during normal states, pathological states (such as cancer), and states such as pregnancy. Exosomes contain a wide variety of proteins, lipids, RNAs, non-transcribed RNAs, miRNAs, and small RNAs (Yin et al, 2013;Becker et al, 2016). Ongoing efforts have shown that miRNAs are secreted into tumor microenvironments to regulate cancer cell proliferation, migration, immune response, intercellular communication, and stromal modification, thereby promoting tumor growth and progression (Meckes et al, 2010;Zhang et al, 2015b;Li et al, 2016).…”

Unexpected gain of function for the scaffolding protein plectin due to mislocalization in pancreatic cancer

“…In assessing whether normal cells that produce abundant exosomes (JAWSII immature dendritic cells) (20) or cells that are rich in cytosolic plectin (keratinocyte, melanocyte, and C6 glioma) (21,22) also have plectin on their cell surface (Fig. S1D), we found that, unlike PDAC cells, these types of cells did not exhibit PTP surface binding.…”

The modulation of co-stimulatory molecules by circulating exosomes in primary biliary cirrhosis

“…[34][35][36][37] In autoimmunity, it has also been suggested that exosomes play a role in the chronic inflammatory response and that the cellular origin of exosomes will differentially influence the immune response in autoimmune disease. 6,38,39 Our data are important because they emphasize that co-stimulatory molecules play a pivotal role in APC-mediated immune responses, particularly T-cell activation and proliferation. [40][41][42][43][44][45] In the study herein, we demonstrate the ability of autologous exosomes to be taken up by peripheral monocytes and DCs.…”