Applications Exosomes in Inflammatory Diseases

Frontiers in Immunology. 2023 Mar 14; 14: 1153901.

Authors: Yang Y, Peng Y, Li Y, Shi T, Luan Y, Yin C.

INTRODUCTION

Exosomes are spherical vesicles composed of a double layer of lipid membranes, 40-160 nm in diameter, and are the most studied extracellular vehicles (EVs) type at present. Most cells in the body can secrete exosomes, such as MSCs, natural killer and T lymphocyte cells, and neutrophils, which have many of the distinctive features of their parent cells, but also have their unique characteristics, containing biologically active macromolecules such as DNA, RNA, nucleic acids, proteins and lipids, and regulates the function of receptor cells by transferring these substances to other receptor cells.

Exosomes and Liver Fibrosis

Liver fibrosis is an imbalance between the synthesis and degradation of the liver’s extracellular matrix (such as collagen glycoproteins and proteoglycans) that progresses further into liver cirrhosis. Exosomes alleviate liver fibrosis by reducing inflammation and promoting liver tissue repair.
Exosomes can reduce liver fibrosis by inhibiting the production of inflammatory factors such as interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α), and pro-fibrotic transforming growth factor-β1 in Kupffer cells. Exosomes also contain miRNAs, such as miRNA-181-5, miR-690, miR-223, and miR-122, which have antifibrotic effects in liver fibrosis.

Exosomes and Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is a non-specific inflammatory disease of the intestine involving the ileum, rectum, and colon mediated by abnormal immunity and infection. Macrophages are important in maintaining intestinal homeostasis, they are involved in the regulation of BD pathogenesis, and some evidence supports the ability of exosomes to activate macrophages.
These exosomes are enriched with proteins involved in the regulation of biological processes in anti-colitis, in particular metallothionein-2, which is necessary for the suppression of inflammatory responses thereby attenuating colitis. In addition to proteins, exosome-mediated miRNAs play an important role in IBD. Exosome miRNAs coordinate the immune system by regulating the functions of T cells, dendritic cells (DCs), macrophages, and NF-κB-related signaling pathways.

Exosomes and Acute Lung Injury

Recently, an increasing number of reports have shown that exosomes play an important role in tissue repair, immune response, and reduction of pro-inflammatory cytokines in sepsis and non-sepsis-induced acute lung injury (ALI).
MSCs-derived exosomes could alleviate sepsis-induced lung injury by inhibiting the release of IL-27, suppressing the expression of pro-inflammatory factors IL-6, IL-1β, and TNF-α, and inhibiting the aggregation of pulmonary macrophages. Exosomes not only play an anti-inflammatory role but also regulate apoptosis.

Exosomes and Atherosclerosis

Atherosclerosis is an inflammatory disease of the blood vessels, and impaired lipid metabolism is the basis of atherosclerosis. Exosomes can be used not only as biomarkers for the diagnosis of atherosclerosis but also as potential therapeutic targets for atherosclerosis.
Macrophages differentiated from monocytes play an important role in atherosclerosis, and macrophage-derived exosomes are involved in the whole process of atherosclerosis. In addition to macrophages, vascular smooth muscle cells (VSMC)-derived exosomes are also key regulators of atherosclerosis.

Exosomes and Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic, predominantly inflammatory synovitis systemic disease of unknown etiology. MSCs-derived exosomes are beneficial in treating RA by reducing bone destruction and erosion, joint inflammation, and mitigating the formation of panniculitis through immunomodulation, anti-inflammation, and differentiation.

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