Background/Purpose: Primary Sjögren’s disease (pSD) is characterized by lymphocytic infiltration of the salivary and lacrimal glands, leading to functional loss and gradually causing dry mouth and dry eyes. In this study, we investigated the anti-inflammatory effects of umbilical cord-derived mesenchymal stem cells (MSCs) on salivary gland pathology and the involvement of Bach2.

Methods: Peripheral blood mononuclear cells (PBMCs) from pSD patients were co-cultured with MSCs under various stimulatory conditions to evaluate the inhibition of cell differentiation and cytokine production. CD4+ T cells and B cells were isolated from the peripheral blood of pSD patients and co-cultured with MSCs stimulated with pSD-associated autoantigens. The changes in cell subsets and the suppression of IgG production due to MSC inhibitory effects were evaluated. Cell damage was induced in human salivary gland cell lines (HSGs) using H2O2, and the frequency of dead cells was compared. The above experiment was performed under conditions with and without contact cell-to-cell. Bach2 expression in T cells, B cells, and monocytes was also evaluated by Western blotting.

Results: MSCs decreased the production of IFN-γ and IL-4 on T cells and TNF-α on monocytes without cell-to-cell contact with MSCs. Co-culturing B cells from pSD patients with MSCs in the presence of CpG-ODN significantly reduced the proportion of plasma cells and increased the proportion of memory B cells compared to B cell monocultures. Similar results were obtained under non-contact cell-to-cell conditions. Furthermore, when CD4⁺T cells and B cells were co-cultured in the presence of pSD-associated autoantigen, IgG production was suppressed under cell-to-cell contact with MSCs compared to without MSCs. In the induction of cell damage against HSGs, the frequency of dead cells was significantly reduced under non-contact with MSCs. In addition, Bach2 expression in T cells, B cells, and monocytes was enhanced when co-cultured with MSCs in the presence of various stimulations.

Conclusion: In this study, we found that the critical function of MSCs is to induce Bach2 expression in target cells through cell-independent, soluble factors. MSCs control cytokine production and excessive autoantibody production in target cells by inducing Bach2 expression, and even prevent cell death in salivary gland cells. Conventional pSD therapy has not achieved sufficient improvement in salivary gland secretion flow through the use of immunosuppressive drugs. MSCs hold potential as an innovative pSD therapy, including for salivary gland disorders.

« Back to ACR Convergence 2025

ACR Meeting Abstracts - https://acrabstracts.org/abstract/umbilical-cord-derived-mesenchymal-stem-cells-suppress-the-pathogenesis-of-primary-sjogrens-disease-by-inducing-bach2-expression/