Cooperative role of MDSCs and Tregs in alum-induced alloimmune tolerance in corneal transplantation.

Alum, a widely used adjuvant, has recently been recognized for its capacity to modulate immune responses beyond classical activation. In this study, we investigated whether alum-induced expansion of myeloid-derived suppressor cells (MDSCs) and their interaction with regulatory T cells (Tregs) promote immune tolerance in corneal transplantation. C57BL/6 mice received repeated intraperitoneal alum injections to induce MDSCs, which were subsequently characterized and tested in suppression assays. Corneal allograft recipients were treated with alum, adoptive transfer of alum-induced MDSCs, or combined transfer of MDSCs and Tregs. Alum significantly expanded MDSCs in the spleen, blood, and bone marrow, and suppressed CD4⁺ T cell proliferation. Compared with MDSCs transfer alone, alum treatment more effectively prolonged allograft survival (50% vs. 20% tolerance), increased Foxp3⁺ Tregs and IL-10⁺ Treg cells, and reduced Th17 responses. Co-transfer of MDSCs and Tregs further enhanced graft survival (~ 60%), indicating a synergistic effect. These findings suggest that alum enhances transplant tolerance through both expansion and activation of MDSCs and Tregs, providing mechanistic insight into its immunosuppressive potential and offering a rationale for combined cell-based strategies in transplantation.