title: The Macrophage Galactose-Type C-Type Lectin (MGL) Modulates Regulatory T Cell Functions.
abstract: 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.
authors.affiliation: Department of Experimental Medicine, "Sapienza" University, Rome, Italy.
authors.forename: Ilaria Grazia
authors.initials: IG
authors.lastname: Zizzari
authors.affiliation: Department of Experimental Medicine, "Sapienza" University, Rome, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Martufi
authors.affiliation: Department of Experimental Medicine, "Sapienza" University, Rome, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Battisti
authors.affiliation: Department of Experimental Medicine, "Sapienza" University, Rome, Italy.
authors.forename: Hassan
authors.initials: H
authors.lastname: Rahimi
authors.affiliation: Department of Experimental Medicine, "Sapienza" University, Rome, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Caponnetto
authors.affiliation: Department of Obstetrics and Gynecology, "Sapienza" University, Rome, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Bellati
authors.affiliation: Department of Experimental Medicine, "Sapienza" University, Rome, Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: Nuti
authors.affiliation: Department of Experimental Medicine, "Sapienza" University, Rome, Italy.
authors.forename: Aurelia
authors.initials: A
authors.lastname: Rughetti
authors.affiliation: Department of Experimental Medicine, "Sapienza" University, Rome, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Napoletano
mesh_terms: D018920:Coculture Techniques; D051858:Forkhead Transcription Factors / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D037181:Lectins, C-Type / Q000276:immunology*; D017493:Leukocyte Common Antigens / Q000276:immunology; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000276:immunology
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D037181:Lectins, C-Type; C506225:MGL lectin, human; D011948:Receptors, Antigen, T-Cell; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051746:ZAP-70 Protein-Tyrosine Kinase; D017493:Leukocyte Common Antigens