THU0075 MIR-21 IN EXOSOMES DRIVED FROM DENTAL PULP STEM CELLS AMELIORATE THE TREGS/TH17 IMMUNE RESPONSE VIA TARGETING STAT3 IN COLLAGEN-INDUCED ARTHRITIS MICE
Authors: Z. Zhang, J. Ji, C. Dong, Z. Gu
Journal: Annals of the Rheumatic Diseases (2020)

Background: Rheumatoid arthritis (RA) is a common and systemic autoimmune disease 1 .It is vital for deciphering pathogenesis to define the precise CD4 + Tcell subsets that are expanded or dysregulated in RA patients 2 .An increase in the Th17 cell subset and a decrease in Tregs resulting imbalance of Tregs/Th17 may be responsible for the occurrence and development of RA 3 . Dental pulp stem cells (DPSCs) appear be a new therapeutic tool for immunological diseases 4,5 .InRA, the mechanism of the effect of miR-21 drivedfromDPSCsexosomes (DPSCs-exo) on the balance of Tregs/Th17 is still unclear. Objectives: We explored the effect of exosomes drived from DPSCson RA and investigated the correlation between DPSCs-exo and Tregs/Th17 balance. Methods: Exosomes were isolated through differential centrifugation. Collagen-induced arthritis(CIA) mice were builded to detect histological change and Tregs/Th17 ratio.CD4 + Tcells were isolated from PBMCs. Exosomes and CD4 + T cells were co-cultured to study the regulation of Tregs/Th17 balance.The relationship between miR-21 and Tregs/Th17 balance was studied by flow cytometry, qRT-PCR and Western blotting etc. Results: After Dpscs-exo treatment, the clinical scores and paw swelling of CIA mice decreased.At the same time, the expression of Treg cells increased and the expression of Th17 cells decreased in the spleen,changing the ratio of Tregs/Th17.Exosomes and CD4 + T cells were co-culture,showing that Treg cellsincreased and Th17 cellsdecreased. MiR-21 is highly expressed in RA patients.MiR-21 in exosomes were Knockout and overexpressed.The balance ofTregs/Th17 decreased when miR-21 were knockout and increased when miR-21were overexpressed. In addition, STAT3 in CD4 + T cells were overexpressed and co-culture with DPSCs-exo,which inhibited Tregs/Th17. Conclusion: We elucidated the mechanism of the regulation of Tregs/Th17 balance by DPSCs-exo, that is, miR-21 in exosomes drived from dental pulp stem cells ameliorate the Tregs /Th17 immune response via targeting STAT3 in collagen-induced arthritis mice. References: [1]MF, B. et al. Hexokinase 2 as a novel selective metabolic target for rheumatoid arthritis. 77 , 1636-1643, doi: 10.1136/annrheumdis-2018-213103 (2018). [2]CY, F. et al. Mixed-effects association of single cells identifies an expanded effector CD4 T cell subset in rheumatoid arthritis. 10 , doi: 10.1126/scitranslmed.aaq0305 (2018). [3]Q, S. et al. Impaired Tip60-mediated Foxp3 acetylation attenuates regulatory T cell development in rheumatoid arthritis. 100 , 27-39, doi: 10.1016/j.jaut.2019.02.007 (2019). [4]L, J. et al. Comparison of immunomodulatory properties of exosomes derived from bone marrow mesenchymal stem cells and dental pulp stem cells. 67 , 432-442, doi: 10.1007/s12026-019-09088-6 (2019). [5]B, M., A, L., M, B., W, L. &amp; cells, S. B. J. S. Concise Review: Dental Pulp Stem Cells: A Novel Cell Therapy for Retinal and Central Nervous System Repair. 35 , 61-67, doi: 10.1002/stem.2398 (2017). Disclosure of Interests: None declared