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.
The macrophage Galactose-type C-type Lectin (MGL) modulates regulatory T cell functions
Caponnetto, S;
2015-01-01
Abstract
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
