Exosomes in Systemic Sclerosis: Messengers Between Immune, Vascular and Fibrotic Components?

Abstract

: Systemic sclerosis (SSc) is a rare autoimmune disease, characterized by vasculopathy and fibrosis of the skin and internal organs. This disease is still considered incurable and is associated with a high risk of mortality, which is related to fibrotic events. An early diagnosis is useful for preventing complications, and targeted therapies reduce disease progression and ameliorate patients' quality of life. Nevertheless, there are no validated biomarkers for early diagnosis with predictive prognostic value. Exosomes are membrane vesicles, transporting proteins and nucleic acids that may be delivered to target cells, which influences cellular behavior. They play important roles in cell-cell communication, both in physiological and pathological conditions, and may be useful as circulating biomarkers. Recent evidences suggest a role for these microvesicles in the three main aspects related to the pathogenesis of SSc (immunity, vascular damage, and fibrosis). Moreover, exosomes are of particular interest in the field of nano-delivery and are used as biological carriers. In this review, we report the latest information concerning SSc pathogenesis, clinical aspects of SSc, and current approaches to the treatment of SSc. Furthermore, we indicate a possible role of exosomes in SSc pathogenesis and suggest their potential use as diagnostic and prognostic biomarkers, as well as therapeutic tools.

Keywords: exosomes; miRNA.; rheumatic disease; systemic sclerosis therapies.

Figure 1

Possible role of exosomes in SSc: Messengers between immune, vascular, and fibrotic components. Genetic predisposition and environmental factors contribute to the onset of SSc. SSc is characterized by a progressive and systemic multi-organ fibrosis, which is preceded by vessel vasculopathy, inflammation, and autoimmunity. Exosomes, membrane-surrounded nano-vesicles, are produced by several types of cells (immune cells, endothelial cells, MSCs, fibroblasts, and vascular smooth muscle cells) and are implicated in inter-cellular communication. Exosomes can carry several types of molecules, i.e., DNA, microRNA, and proteins, which are able to regulate different processes in the target cell, thus influencing its behavior. Immune cells produce exosomes that can act on the same immune cells or on the cells of other tissues, such as endothelial cells regulating, for example, the inflammatory processes. MSCs-derived exosomes have immune-modulatory properties, contain miRNAs with anti- or profibrotic activity and regulate the formation of new vessels. Exosomes secreted by vascular smooth muscle cells are up-taken by endothelial cells, influencing the migratory properties of target cells and angiogenesis. Blue arrows mean interconnection between vasculopathy, autoimmunity, and fibrosis; black arrows mean exosomes affecting target cells.