Supplementary file 1_2′-deoxyinosine ameliorates multiple sclerosis through modulating Th1/Th2 and Th17/Treg cell balance with potential involvement of AMPK phosphorylation.docx

However, effective treatment for MS remains an unmet need. 2′-deoxyinosine (2′-DI), an endogenous nucleoside, has been implicated in tumorigenesis and immune regulation. This study was performed to investigate whether prophylactic 2′-DI intervention could prevent MS progression and elucidate its action mechanism.</p>Methods<p> 2′-DI was administered to experimental autoimmune encephalomyelitis mice in vivo and cultured peripheral blood samples from MS patients in vitro, followed by pathological analysis, body weight monitoring, and disease severity assessment.

Furthermore, RNA sequencing and serum metabolomics were conducted to explore the underlying regulatory mechanism of 2′-DI.</p>Results<p>Compared with healthy controls, MS patients exhibited significantly reduced 2′-DI levels in peripheral blood. Prophylactic administration of 2′-DI could prevent the progression of MS and mitigate inflammatory infiltration in the EAE mouse model. Immunomodulatory studies revealed that 2'-DI could decrease Th1 and Th17 cells, whereas increase Treg and Th2 cells.