Roles of Regulatory T Cell-Derived Extracellular Vesicles in Human Diseases
Abstract
:1. Introduction
2. The Structure and Composition of Extracellular Vesicles from Treg Cells
2.1. Protein
2.1.1. Common EV Proteins
2.1.2. Treg-EVs Specific Proteins
2.2. Nucleic Acids
2.3. Lipids
3. The Interaction between Treg-EVs and Target Cells
4. The Cellular and Molecular Functions of Treg-EVs
4.1. Apoptosis
4.2. Cytokine Production
4.3. Cell Differentiation
4.4. Cell Proliferation
5. The Roles of Treg-EVs in Human Diseases
5.1. Transplantation Rejection
5.1.1. Kidney Transplantation
5.1.2. Liver Transplantation
5.1.3. Skin Transplantation
5.2. Autoimmune Diseases
5.2.1. Psoriasis
5.2.2. Multiple Sclerosis (MS)
5.2.3. Rheumatoid Arthritis (RA)
5.3. Inflammation
5.4. Cancers
5.5. Other Diseases
6. Application of Treg-EVs in Human Diseases
6.1. Transplantation and Autoimmune Diseases
6.2. Biomarkers for Disease Diagnosis
6.3. Delivery Media
7. Conclusions and Remarks
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Treg-EVs Source | Characterization Method | Size; Markers | Specific Cargo | Treg-EVs Function | Ref. |
---|---|---|---|---|---|
Protein | |||||
Mouse natural Treg cells; murine Treg-cell line with self-specificity (Auto-Treg cells) | EM and flow cytometry | Mean 100 nm; LAMP-1/CD63 and CD81 | Transmembrane proteins: CD4, CD2, MHC class I, high levels of CD73 and CD25, and low level of CTLA-4 | CD73 contributes to Treg suppressive activity through adenosine production | [16] |
Human natural Treg cells | EM, NTA, flow cytometry, ELISA, and Western blot | Mean 150 nm; CD63 and CD81 | Transmembrane proteins: CD25, CD39, CCR4, low levels of CD4 and CTLA-4 | Inhibiting T cell proliferation by unknown mechanism | [26] |
IL-35-producing Treg cells | TEM, NTA, ELISA, and Western blot | 50–200 nm; CD81 | Transmembrane proteins: CD39, CD73, and IL-35 subunits (p35 and Ebi3) | Delivering IL-35 to the surface of B and T cells and induced secondary suppression | [27] |
MicroRNA | |||||
Mouse natural Treg cells | Flow cytometry, dynamic light scatter, and ELISA | 20–100 nm; CD9, CD63, and CD81 | miR-155, let-7b, and let-7d | Inhibiting Th1 cell proliferation and IFN-γ secretion by delivering let-7d | [15] |
Human natural Treg cells | TEM, NTA, Western blot, and flow cytometry | Mean 140 nm; presence of clathrin and absence of calnexin | High levels of miR-150-5p, miR-146a-5p, and miR-21-5p, and low levels of miR-155-5p, miR-106a-5p, and miR-19a-3p | Inhibiting CD4+ T cell proliferation by delivering miR-146a-5p | [28] |
Mouse Treg cells stimulated by dendritic cell | EM and NanoSight | Mean 100 nm; markers NA | Low levels of miR-384-5p and high levels of miR-142-3p and miR-150-5p | Changing DCs cytokine profiles by delivering miR-150-5p and miR-142-3p | [29] |
Diseases and Conditions | Source of Tregs | Tregs Isolation Method | Treg-EVs Isolation Method | Effective Molecule | Roles of Treg-EVs | Reference |
---|---|---|---|---|---|---|
Kidney transplantation | Rat Lymphocytes | FACS | Ultracentrifugation (110,000× g) and 30% sucrose/D2O density cushion | Not determined | Prolonging kidney allograft survival | [18] |
Rat CD4+CD25− regulatory T cells | FACS | Ultracentrifugation (100,000× g) | miR-503 and iNOS | Prolonging kidney allograft survival by inhibiting T cell proliferation | [53] | |
Liver transplantation | Mouse spleen lymphocytes | FACS | Ultracentrifugation (110,000× g) with filtration (0.22 μm) | Not determined | Prolonging liver allograft survival by suppressing CD8+ cytotoxic T lymphocyte proliferation | [61] |
Skin transplantation | Human blood | RosetteSep kit and CD25 Microbeads kit | Ultracentrifugation (100,000× g) with filtration (0.22 μm) and ExoQuick-TC | Not determined | Prolonging skin allograft survival by modify T-effector cell cytokine production | [26] |
Psoriasis | Human peripheral blood mononuclear cells | FACS | Ultracentrifugation (100,000× g), microfiltration (ExoMir Mini kit) and differential precipitation (ExoSpin kit) | Not determined | Associated with psoriasis pathogenesis | [28] |
Multiple sclerosis (MS) | Human peripheral blood mononuclear cells | Dynabead Regulatory CD4+CD25+ T cell kit | Total Exosome Isolation kit | Not determined | Suppressing the proliferation of conventional T cells | [52] |
Rheumatoid arthritis (RA) | TGF-β-induced Treg cells-derived EVs (iTreg-EVs) | FACS | EV isolation kits | miR-449a-5p | Reversing Th17/Treg imbalance to prevent RA progression | [60] |
Intestinal inflammation | Mouse spleen | FACS | Ultracentrifugation (100,000× g) and ExoQuick solution | let-7d | Preventing colitis by inhibiting Th1 cell proliferation | [15] |
Mouse spleen mononuclear cells | Mini-MACS immunomagnetic separation system | Ultracentrifugation (100,000× g) with filtration (0.22 μm) | miR-195a-3p | Alleviating inflammatory bowel disease by promoting proliferation and inhibiting apoptosis of colonicepithelial cells | [58] | |
B16 melanoma | Mouse CD8+CD25+ regulatory T cells | MACS beads immunomagnetic separation system | Ultracentrifugation | Not determined | Suppressing cytotoxic T lymphocyte-mediated immunity against B16 melanoma | [17] |
Acute myocardial infarction (AMI) | Mouse spleen | CD4+CD25+ regulatory T cell isolation kit | Total exosome isolation reagent kit | Not determined | Ameliorating AMI by promoting macrophage M2 polarization | [59] |
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Lin, C.; Guo, J.; Jia, R. Roles of Regulatory T Cell-Derived Extracellular Vesicles in Human Diseases. Int. J. Mol. Sci. 2022, 23, 11206. https://doi.org/10.3390/ijms231911206
Lin C, Guo J, Jia R. Roles of Regulatory T Cell-Derived Extracellular Vesicles in Human Diseases. International Journal of Molecular Sciences. 2022; 23(19):11206. https://doi.org/10.3390/ijms231911206
Chicago/Turabian StyleLin, Can, Jihua Guo, and Rong Jia. 2022. "Roles of Regulatory T Cell-Derived Extracellular Vesicles in Human Diseases" International Journal of Molecular Sciences 23, no. 19: 11206. https://doi.org/10.3390/ijms231911206