Mesenchymal Stem Cells Protect Against Sepsis-associated Acute Kidney Injury by Inducing Gal-9/Tim-3 to Remodel Immune Homeostasis

Abstract Objective: The aim of the present study was to investigate the specific mechanism by which MSCs protect against SA-AKI.Methods: Male C57BL/6 mice underwent cecal ligation and puncture operation to induce sepsis and then received either normal IgG or MSCs (1* 106 cells intravenously) plus Gal-9 or soluble-Tim-3 3h after surgery. Results: After cecal ligation and puncture operation, injection with Gal-9 or MSCs plus Gal-9 had a higher survival rate than the IgG treatment group. Treatment with MSCs plus Gal-9 decreased serum creatinine and blood urea nitrogen levels and improved recovery of tubular function. Reduce the levels of IL-17, RORγt and induce the expression of IL-10 and FOXP3. Additionly, remodel the balance of TH17/Treg. However, when used soluble Tim-3 to block the Gal-9/Tim-3 pathway, the septic mice developed badly kidney injury and exhibited a higher mortality. Treatment with MSCs plus soluble Tim-3 blunted the therapeutic effect of MSCs, and inhibited the induction of Tregs and suppressed the inhibition of the differentiation to Th17 cells.Conclusion: Treatment with MSCs significantly reversed the TH1/TH2 balance. And the important mechanism for MSCs protection against SA-AKI maybe through the Gal-9/Tim-3 pathway.