Inhibition of miR-155 attenuates dendritic cell maturation and skin allograft rejection through SOCS1 in a rhesus monkey model.

Introduction: Modulating dendritic cells (DCs; inhibiting maturation and antigen-presenting capacity) potentially promote immune tolerance to the benefit of allografts. In this study, we aimed to elucidate the impact of miR-155 on DC maturation and allograft rejection.

Material and methods: Donor monkey bone marrow-derived dendritic cells (BMDCs) were transduced with anti-miR-155 lentivirus to inhibit miR-155 expression, and the T cell phenotype and function of DC^anti-155 upon lipopolysaccharide (LPS) stimulation were evaluated. In vivo, imDC, imDC^anti-NC, and imDC^anti-155 were injected into recipient monkeys before skin transplantation. The survival times of skin allografts were recorded and the proportions of T cell subsets in spleen and secretion levels of cytokines in serum were measured. SOCS1/JAK/STAT pathway expression was also examined.

Results: miR-155 level increased during the maturation of dendritic cells. Inhibition of miR-155 significantly attenuated LPS-induced DC maturation. imDC^anti-155 promoted the differentiation of regulatory T cells (Tregs) and augmented the secretion of immunosuppressive cytokines. In vivo, subcutaneous injection of imDC^anti-155 prolonged recipient monkey skin allograft survival times and attenuated immune rejection. An increase in the proportion of Treg cells and their secreted cytokines in serum was observed in the imDC^anti-155 group. Mechanistic insights suggest that miR-155 likely regulates the SOCS1-JAK/STAT pathway.

Conclusions: Suppression of miR-155 has the potential to inhibit DC maturation, affects the differentiation of T cell subsets, and prolongs skin allograft survival, which could serve as a promising therapeutic strategy for managing allograft rejection.