The Macrophage Galactose-Type C-Type Lectin (MGL) Modulates Regulatory T Cell Functions.

Autor: Ilaria Grazia Zizzari, Paola Martufi, Federico Battisti, Hassan Rahimi, Salvatore Caponnetto, Filippo Bellati, Marianna Nuti, Aurelia Rughetti, Chiara Napoletano
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Zdroj: PLoS ONE, Vol 10, Iss 7, p e0132617 (2015)
Druh dokumentu: article
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0132617
Popis: Regulatory T cells (Tregs) are physiologically designed to prevent autoimmune disease and maintain 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 expressed by Tregs and the C-type lectin MGL. This specific interaction strongly decreases the immunosuppressive activity of Tregs, restoring the proliferative capacity of co-cultured T lymphocytes. This effect can be attributed to changes in CD45RA and TCR signalling through the inhibition of Lck and inactivation of Zap-70, 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.
Databáze: Directory of Open Access Journals