title: Hydrogen-bonded multilayers of tannic acid as mediators of T-cell immunity.
abstract: Type 1 diabetes is an autoimmune-mediated disease resulting in the destruction of insulin-secreting pancreatic β-cells. Transplantation of insulin-producing islets is a viable treatment to restore euglycemia in Type 1 diabetics; however, the clinical application remains limited due to the use of toxic immunosuppressive therapies to prevent immune-mediated rejection. A nanothin polymer material with dual antioxidant and immunosuppressive properties capable of modulating both innate and adaptive immune responses crucial for transplantation outcome is presented. Through the use of hollow microparticles (capsules) composed of hydrogen-bonded multilayers of natural polyphenol (tannic acid) with poly(N-vinylpyrrolidone) (TA/PVPON) and with poly(N-vinylcaprolactam) (TA/PVCL), proinflammatory reactive oxygen and nitrogen species are efficiently dissipated and the production of interferon (IFN)-γ and tumor necrosis factor (TNF)-α proinflammatory cytokines is attenuated by cognate antigen-stimulated autoreactive CD4+ T cells. These results provide evidence that TA-containing capsules are efficacious in immunomodulation and may provide physical transplant protection and prevent diabetogenic autoreactive T-cell responses. Future studies will determine if xeno- and allotransplantation with (TA/PVPON)- or (TA/PVCL)-coated pancreatic islets will decrease the risk of graft rejection due to attenuation of oxidative stress and IFN-γ, and restore euglycemia in Type 1 diabetics.
authors.affiliation: Department of Chemistry, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
authors.forename: Veronika
authors.initials: V
authors.lastname: Kozlovskaya
authors.forename: Bing
authors.initials: B
authors.lastname: Xue
authors.forename: Weiqi
authors.initials: W
authors.lastname: Lei
authors.forename: Lindsey E
authors.initials: LE
authors.lastname: Padgett
authors.forename: Hubert M
authors.initials: HM
authors.lastname: Tse
authors.forename: Eugenia
authors.initials: E
authors.lastname: Kharlampieva
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006860:Hydrogen Bonding; D056747:Immunomodulation / Q000187:drug effects; D051379:Mice; D016688:Mice, Inbred NOD; D049329:Nanostructures / Q000737:chemistry; D050797:STAT4 Transcription Factor / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D013634:Tannins / Q000737:chemistry / Q000494:pharmacology*; D046509:Tissue Culture Techniques / Q000379:methods*
chemical_list: D016207:Cytokines; D050797:STAT4 Transcription Factor; C494091:Stat4 protein, mouse; D013634:Tannins
keywords: antioxidants; hydrogen-bonded multilayers; immunomodulatory; poly(N-vinylpyrrolidone); tannic acid; type-1 diabetes