Pos1001 Induced Pluripotent Stem Cell-Derived Mesenchymal Stem Cells Alleviate Sjögren’s Syndrome by Modulating the Maturation Process of Splenic B Cells

Background: Sjogren's Syndrome (SS) is a chronic systemic autoimmune disease characterized by the development of lymphocyte infiltration lesions in salivary and lacrimal glands, leading to disruption of their secretory function. This results in clinical manifestations such as xerostomia and dry eye, significantly impacting patients' quality of life. Unfortunately, effective treatment options for this condition are extremely limited. Mesenchymal stem cells (MSCs) and their derivatives hold great promise as potential therapeutic strategies for SS due to their remarkable immunoregulatory capacity. However, the underlying mechanisms responsible for these beneficial effects remain poorly understood. Objectives: Therefore, the objective of this study is to elucidate the specific mechanism through which induced pluripotent stem cell-derived MSCs (iMSCs) therapy can effectively regulate immunoregulation in the treatment of SS. Methods: MSCs were administered intravenously via the tail vein into NOD/ShiLtJ mice, a spontaneous SS model. The salivary flow rate (SFR) was quantified, while lymphatic infiltration in the submandibular gland was assessed using HE staining. Additionally, immunofluorescence staining was employed to evaluate T cell and B cell infiltration in the submandibular gland, whereas flow cytometry was utilized to detect T cells and B cells in the spleen. Results: Compared to the ICR mice, the NOD/ShiLtJ mice exhibited a decrease in SFR, which was subsequently recovered after iMSC treatment. Histological examination using HE staining revealed the absence of lymphocyte infiltration foci in the ICR mice, extensive lymphocyte infiltration foci in the NOD/ShiLtJ mice, and reduced lymphocyte infiltration following iMSC treatment. Analysis of the number and area ratio of lymphocyte infiltration foci indicated that iMSCs inhibited their formation. Furthermore, immunofluorescence staining for CD19 and CD3 in submandibular glands revealed a significant decrease in both T cells (CD3-positive cells) and B cells (CD19-positive cells) following iMSC treatment. Moreover, flow cytometry analysis of mouse spleen demonstrated an aberrant expansion of marginal zone B cells (MZB, B220+CD21hiCD23lo), which are mature B cells, as well as a down-regulation of transitional B cells (TRB, B220+CD21-CD23-) in NOD/ShiLtJ mice. Treatment with iMSCs resulted in a reduced proportion of MZB cells and an increased proportion of TRB cells. Conclusion: Our fundings support the notion that iMSCs exhibit a protective effect against SS by inhibiting the maturation of B cells, thereby establishing a theoretical basis for comprehending the role of iMSCs in SS. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: None declared.