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 / Zizzari, Ig; Martufi, Paola; Battisti, F; Rahimi Koshkaki, H; Caponnetto, S; Bellati, F; Nuti, M; Rughetti, A; Napoletano, C.. - In: PLOS ONE. - ISSN 1932-6203. - ELETTRONICO. - 10:7(2015). [10.1371/journal.pone.0132617]
The macrophage Galactose-type C-type Lectin (MGL) modulates regulatory T cell functions
Zizzari, IgPrimo
;Rahimi Koshkaki, H;Caponnetto, S;Bellati, F;Nuti, M
;Rughetti, APenultimo
;Napoletano, C.Ultimo
2015
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.File | Dimensione | Formato | |
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Zizzari_ The Macrophage Galactose_2015.pdf
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Note: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0132617
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