Amisha Patel

Introduction: Rheumatoid Arthritis (RA) is a chronic inflammatory disease in the joints that negatively impacts bone constitution, mobility, and overall quality of life.¹ The presence of helper T cells (Th17) cells, and downregulation of regulatory T cells (Treg) cells, in inflammation sites, is a prominent feature of Rheumatoid Arthritis (RA). Studies demonstrate that mesenchymal stem cells (MSCs) play an important modulatory role in regulating the Th17/Treg ratio, mitigating the pathogenic effects in autoimmune diseases.² Methods: The effects of human umbilical cord mesenchymal stem cells (hUCMSCs) on RORγt and Foxp3 expression, and Th17/Treg cell ratios were evaluated in collagen-induced arthritis rats in a preclinical model using cell culture and flow cytometry.² To determine the mechanisms by which MSCs exert the immunomodulatory effects, MSCs overexpressing or knockdown A20 were used in co-cultures.³ Also, Inducible T cell Costimulator Ligand (ICOSL) interaction with Inducible T cell Costimulator (ICOS) and its contact-dependent mechanism of upregulating Treg cells was evaluated. ⁴ In a clinical case study, a single dose of autologous MSCs isolated from bone marrow was injected intravenously into 13 patients suffering from refractory RA. Levels of Foxp3, and the IL-10 and TGF-β cytokines of Tregs were evaluated.⁵ Results: The results showed that hUCMSCs have therapeutic effects in mitigating inflammation factors involved in RA. hUCMSCs suppressed T lymphocyte proliferation, and Th17 cell ratio, and increased Treg cell ratio in an A20-dependent manner.^2-3 Also, when ICOSL was inhibited in MSCs, Treg levels were significantly reduced.⁴ Finally, a clinical study verified the clinical effects of MSCs by demonstrating decreased Th17/Treg ratios and increased anti-inflammatory cytokines in patients with refractory RA.⁵ Conclusion: MSCs altered the Th17/Treg ratio to favor upregulation of Tregs and downregulation of Th17 cells, and A20 and ICOSL are major factors responsible for the MSC-mediated immunomodulation. These results strongly support the therapeutic potential of MSCs for the treatment of RA.

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2. Ma D, Xu K, Zhang G, et al. Immunomodulatory effect of human umbilical cord mesenchymal stem cells on T lymphocytes in rheumatoid arthritis. Int Immunopharmacol. 2019;74:105687. doi:10.1016/j.intimp.2019.105687
3. Feng Z, Zhai Y, Zheng Z, et al. Loss of A20 in BM-MSCs regulates the Th17/Treg balance in Rheumatoid Arthritis. Sci Rep. 2018;8(1):427. Published 2018 Jan 11. doi:10.1038/s41598-017-18693-0
4. Lee HJ, Kim SN, Jeon MS, Yi T, Song SU. ICOSL expression in human bone marrow-derived mesenchymal stem cells promotes induction of regulatory T cells. Sci Rep. 2017;7:44486. Published 2017 Mar 14. doi:10.1038/srep44486
5. Ghoryani M, Shariati-Sarabi Z, Tavakkol-Afshari J, Mohammadi M. The Sufficient Immunoregulatory Effect of Autologous Bone Marrow-Derived Mesenchymal Stem Cell Transplantation on Regulatory T Cells in Patients with Refractory Rheumatoid Arthritis. J Immunol Res. 2020;2020:3562753. Published 2020 Apr 28. doi:10.1155/2020/3562753