This review highlights the significant potential of MSCs and their EVs as therapeutic tools for regulating CD4⁺T cells in immune diseases. Further research and clinical trials are crucial for translating these findings into effective and safe treatments for patients.
Key Findings:
MSCs and EVs regulate CD4⁺T cells through various mechanisms, including:
Secretion of soluble factors: MSCs release bioactive molecules like IDO1, TGF-β1, and miR-139 that directly impact CD4⁺T cell proliferation and differentiation.
Direct cell-cell contact: MSCs interact with CD4⁺T cells through cell surface receptors, influencing their behavior and function.
EV-mediated communication: MSC-derived EVs carry bioactive molecules, including proteins, lipids, and nucleic acids, that regulate CD4⁺T cell phenotype and function.
MSCs and EVs demonstrate therapeutic potential in various immune diseases:
Systemic Lupus Erythematosus (SLE): MSCs and EVs modulate the balance of Th1, Th2, Th17, Treg, and TFH cells, leading to reduced inflammation and improved kidney function.
Rheumatoid Arthritis (RA): MSCs and EVs suppress Th1 and Th17 cells while promoting Treg cells, alleviating joint inflammation and symptoms.
Allergic Diseases: MSCs and EVs reduce Th2 cell infiltration and inflammation in the lungs, improving asthma and allergic rhinitis symptoms.
Graft-Versus-Host Disease (GVHD): MSCs and EVs restore immune balance by promoting Treg cell proliferation and inhibiting Th1 and Th17 cell activity, reducing GVHD severity.
Autoimmune Meningitis: MSCs and EVs inhibit Th1 and Th17 cells while promoting Treg cell differentiation, ameliorating central nervous system inflammation and symptoms.
Safety considerations: While MSCs and EVs hold great promise, further research is needed to address potential safety concerns and optimize their therapeutic application.

Future Perspectives:

1. Understanding the specific mechanisms of MSC and EV-mediated immunomodulation.
2. Developing strategies to improve MSC and EV safety and efficacy.
3. Exploring the potential of MSC and EV-based therapies for other immune diseases.
4. Investigating the role of MSCs and EVs in modulating Th22 cells in immune diseases.

The work entitled “Mechanism and application of mesenchymal stem cells and their secreting extracellular vesicles in regulating CD4⁺T cells in immune diseases”was published on Biophysics Reports (published on December, 2024).
DOI: 10.52601/bpr.2024.240005