Immune Modulation Using Extracellular Vesicles Encapsulated with MicroRNAs as Novel Drug Delivery Systems

Abstract

Self-tolerance involves protection from self-reactive B and T cells via negative selection during differentiation, programmed cell death, and inhibition of regulatory T cells. The breakdown of immune tolerance triggers various autoimmune diseases, owing to a lack of distinction between self-antigens and non-self-antigens. Exosomes are non-particles that are approximately 50-130 nm in diameter. Extracellular vesicles can be used for in vivo cell-free transmission to enable intracellular delivery of proteins and nucleic acids, including microRNAs (miRNAs). miRNAs encapsulated in exosomes can regulate the molecular pathways involved in the immune response through post-transcriptional regulation. Herein, we sought to summarize and review the molecular mechanisms whereby exosomal miRNAs modulate the expression of genes involved in the immune response.

Keywords: exosomes; extracellular vesicles; immune modulation; immune regulation via miRNAs; immune tolerance; macrophages.

Figure 1

Autoimmunity and immune tolerance induction in dendritic cells. Through the interaction of dendritic cells (DCs) with T cells via major histocompatibility (MHC)-class I or -class II and co-stimulatory receptors and cytokine secretion levels, pro-inflammatory DCs presenting self-antigen can prime CD8+ helper and CD4+ killer T cells, promoting autoimmune diseases and transplant rejection in autoimmunity. However, the DCs in immune tolerance express specific cytokines and receptors, inducing regulatory T cells or anergy. The expanding natural T regulatory cells (nTregs) induce polyclonal activation with IL-2.

Figure 2

Modulation of immune response by miRNAs. Polarization of macrophages, M1 to M2, differentiated from monocytes, regulated by some molecular pathways, including NF-kB, STAT1, STAT3, and PI3K/Akt pathways, via post-transcriptional regulation by miRNAs, such as miR-155, miR-21, miR-let-7b, miR-145, miR-146a, miR-3473b, miR-23a, and miR-223.