title: Islet antigen-pulsed dendritic cells expressing ectopic IL-35Ig protect nonobese diabetic mice from autoimmune diabetes.
abstract: Dendritic cells (DCs) are professional antigen presenting cells capable of orchestrating either stimulatory or regulatory immune responses mediated by T cells. Interleukin 35 (IL-35) is an immunosuppressive, heterodimeric cytokine belonging to the IL-12 family and known to be produced by regulatory T cells but not DCs. In this study, we explored the possible immunosuppressive effect of IL-35 ectopically expressed by splenic DCs from nonobese diabetic (NOD) mice, a prototypical model of autoimmune diabetes. After pulsing with the IGRP peptide (a dominant, diabetogenic autoantigen in NOD mice) and transfer in vivo, IL-35Ig- but not Ig-transfected DCs suppressed antigen specific, T cell-mediated responses in a skin test assay. More importantly, transfer of IL-35Ig-transfected, IGRP-pulsed DCs into prediabetic NOD mice induced a delayed and less severe form of diabetes, an effect accompanied by the increase of CD4(+)CD39(+) suppressive T cells in pancreatic lymph nodes. Our data therefore suggest that DCs overexpressing ectopic IL-35Ig might represent a powerful tool in negative vaccination strategies.
authors.affiliation: Department of Experimental Medicine, University of Perugia, Piazzale Gambuli 1 - Bldg C, 4th Fl, 06132 Perugia, Italy. Electronic address: giada.mondanelli@studenti.unipg.it.
authors.forename: Giada
authors.initials: G
authors.lastname: Mondanelli
authors.affiliation: Department of Experimental Medicine, University of Perugia, Piazzale Gambuli 1 - Bldg C, 4th Fl, 06132 Perugia, Italy. Electronic address: claudia.volpi@unipg.it.
authors.forename: Claudia
authors.initials: C
authors.lastname: Volpi
authors.affiliation: Department of Experimental Medicine, University of Perugia, Piazzale Gambuli 1 - Bldg C, 4th Fl, 06132 Perugia, Italy. Electronic address: roberta.bianchi@unipg.it.
authors.forename: Roberta
authors.initials: R
authors.lastname: Bianchi
authors.affiliation: Department of Experimental Medicine, University of Perugia, Piazzale Gambuli 1 - Bldg C, 4th Fl, 06132 Perugia, Italy. Electronic address: massimo.allegrucci@unipg.it.
authors.forename: Massimo
authors.initials: M
authors.lastname: Allegrucci
authors.affiliation: Department of Experimental Medicine, University of Perugia, Piazzale Gambuli 1 - Bldg C, 4th Fl, 06132 Perugia, Italy. Electronic address: vincenzo.talesa@unipg.it.
authors.forename: Vincenzo Nicola
authors.initials: VN
authors.lastname: Talesa
authors.affiliation: Department of Experimental Medicine, University of Perugia, Piazzale Gambuli 1 - Bldg C, 4th Fl, 06132 Perugia, Italy. Electronic address: ursula.grohmann@unipg.it.
authors.forename: Ursula
authors.initials: U
authors.lastname: Grohmann
authors.affiliation: Department of Experimental Medicine, University of Perugia, Piazzale Gambuli 1 - Bldg C, 4th Fl, 06132 Perugia, Italy. Electronic address: marialaura.belladonna@unipg.it.
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Belladonna
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000235:genetics* / Q000276:immunology; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000517:prevention & control* / Q000628:therapy; D005260:Female; D015316:Genetic Therapy / Q000379:methods; D057809:HEK293 Cells; D006801:Humans; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D008969:Molecular Sequence Data; D010179:Pancreas / Q000166:cytology / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology
chemical_list: D000906:Antibodies; D007378:Interleukins; D011993:Recombinant Fusion Proteins; C569375:interleukin-35, mouse
keywords: Autoimmune diabetes; Dendritic cells; Engineered cytokines; IL-35; NOD mice