The macrophage Galactose-type C-type Lectin (MGL) modulates regulatory T cell functions

Regulatory T cells (Tregs) are physiologically designed to prevent autoimmune disease and main-tain self-tolerance. In tumour microenvironments, their presence is related to a poor prognosis, and they influence the therapeutic outcome due to their capacity to suppress the immune response by cell-cell contact and to release immunosuppressive cytokines. In this study, we demonstrate that Treg immunosuppressive activity can be modulated by the cross-linking between the CD45RA ex-pressed by Tregs and the C-type lectin MGL. This specific interaction strongly decreases the im-munosuppressive activity of Tregs, restoring the proliferative capacity of co-cultured T lympho-cytes. This effect can be attributed to changes in CD45RA and TCR signalling through the inhibi-tion of Lck and inactivation of Zap70, an increase in the Foxp3 methylation status and, ultimately, the reduced production of suppressive cytokines. These results indicate a role of MGL as an immunomodulator within the tumour microenvironment interfering with Treg functions, suggesting its possible use in the design of anticancer vaccines.