Exosomes: The immune system’s invisible army

Imagine a tiny army of microscopic spherical vesicles – filled with protein, DNA, RNA and metabolites and RNA – circulating within our bodies and being responsible for regulating major physiological processes and diseases. Sounds like something straight out of a science fiction novel, doesn’t it? These vesicles are real and are called exosomes! 

Exosomes – their origin story 

Recent studies in the last two decades have generated considerable interest in exosome biology. Exosomes are a subset of extracellular vesicles released from cells that range between ~40 to 160 nm in diameter—similar in size to a microscopic virus. They are found in body fluids such as plasma, urine, saliva and breast milk. Exosomes are released from almost every cell type, including immune cells like T cells, B cells and neutrophils, indicating that they may carry out functions similar to their parent cells and therefore, influence the host immunity. They can be a highly heterogeneous population and their diverse characteristics can be based on their size, content, functional influence on recipient cells, and their cellular origin. 

Their superpower? They have the capability of inducing a complex biological response in cells. 

Functionally, they act as a message delivery system between cells. The messages come in the form of proteins, genetic material, and other substances, and these biological cargos alter the function of the recipient cell. In the setting of cancer, infection or an autoimmune disease, the exosomes have the ability to change the course of immune response just by the virtue of the cargo they carry. 

Exosomes are tiny extracellular vesicles produced by all cells. Within them, they carry a variety of biological cargo, namely, nucleic acids, proteins, lipids, and metabolites. (Figure created using bioRender). 

How do these tiny spheres impact our mighty and complicated immune system?

In our immune system, exosomes have been shown to participate in diverse immunological processes such as antigen presentation, immune activation as well as suppression, and maintaining immune tolerance. Immune cells can be directly or indirectly influenced by incoming exosomes which can stimulate or suppress their proliferation and/or function. In doing so, exosomes contribute to the development and progression of several diseases. For example, studies have demonstrated that exosomes derived from antigen presenting cells can act as a stimulatory signal for T cell activation. Furthermore, the emerging role of exosomes in antigen presentation was also explored in the context of anti-tumor immunity, viral as well as bacterial infection.

Surprisingly, exosomes do not randomly interact with any neighbouring recipient cell simply because it is accessible. Apparently, they display distinct tissue-specific or cell-specific homing based on their surface marker expression, such as adhesion molecules and integrins. This selective transmission of exosomal information makes them attractive candidates for the diagnosis and treatment of diseases.

Designer exosomes as therapeutics

Since they carry biological material to neighbouring and distant cells in a defined manner, they have been viewed as useful vectors that can be directed to carry specific drugs or other therapeutic cargo. In contrast to other available vectors, that are mainly composed of synthetic polymers, exosomes are made of cell membranes and are, therefore, more easily accepted by the host. Exosomes can be chemically or biologically modified to enhance, broaden or change their configuration to increase their effectiveness. There are multiple strategies for exosome modification. An example of indirect exosome modification is when exogenous material is introduced to exosomes using micelles that fuse with target cytoplasmic membranes. Exosomes can also be directly modified by permeabilizing their membrane so as to introduce desired cargo within them. 

Although harnessing the potential of exosomes can be extremely rewarding and can have tremendous benefits in the field of therapeutics, scientists still face a multitude of obstacles in engineering exosomes to be the ideal candidate for therapeutics. For example, non-specific biodistribution and uptake of exosomes into non-target organs or tissues pose a huge challenge for exosome-based drug delivery. Additionally, after in vivo administration of exosomes, they have been shown to be rapidly cleared from the circulation. Therefore, there is definitely room for improvement and scientists are trying to optimize their use as therapeutic vectors in several disorders such as cancer, Alzheimer’s disease and viral infections, to name a few. 

In summary, exosomes are one of the key mediators of cellular communication that influence various immune regulatory processes. These distinct and valuable features are being utilized by researchers to harness the therapeutic potential of exosomes in various diseases such as cancer. The study of exosomes is a highly dynamic and active area of research. More work is required to decipher the complex function of exosomes and to study their applications, however, exciting recent advances hold promise to bring profound changes in the field of therapeutic and personalized medicine.

Featured image: “Exosomes on surface of HeLa cell” licensed under CC BY 4.0

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