title: An antigen-encapsulating nanoparticle platform for TH1/17 immune tolerance therapy.
abstract: Tolerogenic nanoparticles (NPs) are rapidly being developed as specific immunotherapies to treat autoimmune disease. However, many NP-based therapies conjugate antigen (Ag) directly to the NP posing safety concerns due to antibody binding or require the co-delivery of immunosuppressants to induce tolerance. Here, we developed Ag encapsulated NPs comprised of poly(lactide-co-glycolide) [PLG(Ag)] and investigated the mechanism of action for Ag-specific tolerance induction in an autoimmune model of T helper type 1/17 dysfunction - relapse-remitting experimental autoimmune encephalomyelitis (R-EAE). PLG(Ag) completely abrogated disease induction in an organ specific manner, where the spleen was dispensable for tolerance induction. PLG(Ag) delivered intravenously distributed to the liver, associated with macrophages, and recruited Ag-specific T cells. Furthermore, programmed death ligand 1 (PD-L1) was increased on Ag presenting cells and PD-1 blockade lessened tolerance induction. The robust promotion of tolerance by PLG(Ag) without co-delivery of immunosuppressive drugs, suggests that these NPs effectively deliver antigen to endogenous tolerogenic pathways.
authors.affiliation: Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
authors.forename: Derrick P
authors.initials: DP
authors.lastname: McCarthy
authors.affiliation: Department of Biomedical Engineering, Evanston, IL, USA.
authors.forename: Jonathan Woon-Teck
authors.initials: JW
authors.lastname: Yap
authors.affiliation: Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Harp
authors.affiliation: Department of Chemical and Biological Engineering, Evanston, IL, USA.
authors.forename: W Kelsey
authors.initials: WK
authors.lastname: Song
authors.affiliation: Department of Chemical and Biological Engineering, Evanston, IL, USA.
authors.forename: Jeane
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Pearson
authors.affiliation: Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; Chemistry of Life Processes Institute (CLP), Northwestern University, Evanston, IL, USA; The Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA. Electronic address: s-d-miller@northwestern.edu.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Miller
authors.affiliation: Department of Biomedical Engineering, Evanston, IL, USA; Department of Chemical and Biological Engineering, Evanston, IL, USA; Chemistry of Life Processes Institute (CLP), Northwestern University, Evanston, IL, USA; The Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA; Department of Obstetrics and Gynecology, Northwestern University, Chicago, IL, USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA; Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA. Electronic address: ldshea@umich.edu.
authors.forename: Lonnie D
authors.initials: LD
authors.lastname: Shea
mesh_terms: D000818:Animals; D000941:Antigens / Q000008:administration & dosage; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000628:therapy*; D007108:Immune Tolerance; D007167:Immunotherapy; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D011098:Polyglactin 910 / Q000737:chemistry; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology; D013154:Spleen / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D000941:Antigens; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D011098:Polyglactin 910
keywords: Autoimmune disease; Drug delivery; Immune tolerance; Nanoparticle