Exosomes mediate intercellular communication and regulate biological activity. Exosomes are involved in the pathogenesis of several autoimmune diseases. Exosome-derived miRNAs mediate the functions of exosomes. Immunomodulation is about to become an important therapy for the treatment of many diseases, due to the important role of the immune system in the defense of the human body.
Although the immune system is an essential defense system, hyperactivity can cause a variety of diseases, such as inflammation and autoimmune diseases. Exosomes are becoming a cutting-edge therapeutic strategy for treating an overactive immune system. Therefore, in this review, we will thoroughly review the therapeutic applications of exosomes in various inflammatory and autoimmune diseases. Finally, issues will be presented related to the prospects for the future of exosomal therapy. Exosomes are extracellular microvesicles (30-150 nm) released by cells that contain proteins, lipids, RNA and DNA.
They can carry bioactive molecules and act as carriers that facilitate communication between cells, such as antigen presentation, inflammatory activation, autoimmune diseases (AIDS) and tumor metastasis. Recently, much attention has been paid to the biology and functions of exosomes in immune regulation and AIDS, including autoimmune thyroid diseases (AITD). Some studies have shown that exosomes are involved in the appearance and development of AITDs, but they are still found in the preliminary phase of exploration. This review mainly presents the association of exosomes with immune regulation and emphasizes the potential role of exosomes in AITDs, with the objective of providing new strategies and research guidelines for the pathogenesis and early diagnosis of AITDs.
There is increasing evidence that exosomes are involved in establishing an inflammatory response and in modulating the immune system.
Exosome-derived
miRNAs affect gene expression in immune cells, and exosomes have other immunological functions, including the activation of effector immune cells (e.g., differential expression patterns of exosome-derived miRNAs have been described in autoimmune conditions, and miRNAs have been implicated in the pathogenesis of many of these conditions, such as psoriasis, inflammatory bowel disease (IBD), type 1 diabetes, multiple sclerosis (MS) and systemic lupus erythematosus (SLE).), rheumatoid arthritis (RA), Sjögren's syndrome (SS), systemic sclerosis (SSc), graft-versus-host disease (GVHD), and autoimmune thyroid diseases (AITD).The use of exosome-derived miRNAs as biomarkers of autoimmune diseases offers an early and non-invasive diagnostic option. Exosomes can be isolated from many biological fluids, such as blood, saliva, and urine. Usually, serum from patients' blood samples can be tested for the presence of specific exosome components, and exosomes have already been used as biomarkers for cancer, hepatitis C and Alzheimer's disease.Now, researchers are studying its usefulness as a diagnostic biomarker to provide diagnoses earlier of autoimmune diseases. As mentioned above, exosomes derived from MSCs exert immunomodulatory effects through communication interactions with immune cells, which further influences the expression levels of immunoreactive molecules, and this multifunctional modulatory capacity to act simultaneously on the natural and adaptive immune system may partially explain their strong therapeutic potential. Macrophages occupy an important position in the innate immune system and can be classified into pro-inflammatory M1 and anti-inflammatory M2 phenotypes. Recent studies have demonstrated that the anti-inflammatory effects of MSC-derived exosomes are closely related to macrophage polarization, as demonstrated by the inhibition of M1 activation and the induction of the M2 immunosuppressive phenotype (3).
In addition, the reduction of in vivo levels of immunoreactive substances such as IL22 and Th17, together with the upregulation of IL10, ultimately led to the suppression of inflammation in macrophages (39, 40). In addition, all exosomes derived from MSCs have the capacity to inhibit the activation and proliferation processes of natural immune cells, such as NK and DC, thus exerting immunosuppressive effects and attenuating toxic inflammatory responses (41, 4). On the other hand, like the main immune cells of the adaptive immune system, both B cells and T cells were regulated by exosomes derived from MSCs, which in turn affected humoral and cellular functions. immunity. MSCs inhibited antibody secretion, activation and proliferation of B cells and, oddly enough, this regulatory effect could be perfectly inherited by exosomes derived from MSCs (4).
At the same time, the level of secretion of regulatory B cells, an important functional subpopulation, was significantly up-regulated by exosomes, resulting in the release of large amounts of anti-inflammatory factors such as IL-10 (4). T cells are important effector immune cells involved in autoimmune cells. diseases. Exosomes alleviate the progression of most autoimmune diseases by inhibiting T cell activation and proliferation.
However, their role in regulating the proportion of helper T cells of different phenotypes is also crucial. The dynamic balance between Th1 and Th2 is closely related to the activation or suppression of inflammation. In addition, increasing the proportion of Treg and the induction of apoptosis in activated T cells also contribute significantly to disease prevention and delayed progression (45, 4). Therefore, exosomes have aroused great interest because of their potential clinical applications in the treatment of diseases associated with abnormal immune regulation.
In addition, researching more bioactive nano-coated materials to improve the selection and utilization of exosomes is an important design factor (60). Using metabolic engineering approaches, exosomes can be modified by covalently attaching surface acid groups to diphenylcyclooctine-dithiophosphate. The source of exosomes with a therapeutic effect comes from various sources, such as such as cell culture media. Generating exosomal signatures for diseases such as rheumatoid arthritis and SLE will help healthcare providers provide personalized care.
These genetically engineered exosomes improve the effective concentration and uniform distribution of kartogenin within cells, thus further accelerating the process of cartilage formation in stem stem cells. The role of exosomes in adaptive immunity is to influence the activation, proliferation and apoptosis of T and B cells. Exosomes, characterized by small vesicles adorned with molecular markers, mediate the transfer of molecules such as miRNA and proteins to target cells. By precisely manipulating the charge and surface markers of exosomes, designed exosomes have acquired greater anti-inflammatory, immunomodulatory and tissue repair capacity, providing new perspectives for the treatment of autoimmune diseases.
Similarly, another study found that the level of HSP60 in exosomes derived from thyroid follicular cells stimulated by IFN-gamma was significantly higher than in normal exosomes derived from thyrocytes. Circulating exosomes from patients with gestational diabetes were found to be immunologically active and capable of inducing the production of inflammatory cytokines from healthy stem stem cells. Other studies have also demonstrated that (5) exosomes derived from human umbilical cord mesenchymal stem cells can inhibit abnormal cell proliferation CD4+ T and its apoptosis. Exosomes derived from bone marrow mesenchymal stromal cells promote remyelination and reduce neuroinflammation in the demyelinating central nervous system.
An increase in IFN-α secretion by plasmacytoid dendritic cells (PDCs) found in the blood was observed in response to microRNAs carried by exosomes in patients with SLE. Autoimmune diseases are caused by an imbalance in the immune system, which produces autoantibodies that cause inflammation, causing tissue damage and organ dysfunction.
