Localized immunosuppression with tannic acid encapsulation delays islet allograft and autoimmune-mediated rejection
figureposted on 25.06.2020 by Ada Admin, Jessie M. Barra, Veronika Kozlovskaya, Eugenia Kharlampieva2, Hubert M. Tse
Figures are generally photos, graphs and static images that would be represented in traditional pdf publications.
Type 1 diabetes (T1D) is an autoimmune disease of insulin-producing β-cells. Islet transplantation is a promising treatment for T1D, but long-term graft viability and function remain challenging. Oxidative stress plays a key role in the activation of alloreactive and autoreactive immunity toward the engrafted islets. Therefore, targeting these pathways by encapsulating islets with an antioxidant may delay immune-mediated rejection. Utilizing a layer-by-layer approach, we generated nanothin encapsulation materials containing tannic acid (TA), a polyphenolic compound with redox scavenging and anti-inflammatory effects, and poly(N-vinylpyrrolidone) (PVPON), a biocompatible polymer. We hypothesize that transplantation of (PVPON/TA)-encapsulated allogeneic C57BL/6 islets into diabetic NOD mice will prolong graft function and elicit localized immunosuppression. In the absence of systemic immunosuppression, diabetic recipients containing (PVPON/TA)-encapsulated islets maintained euglycemia and delayed graft rejection significantly longer than non-encapsulated islets. Transplantation of (PVPON/TA)-encapsulated islets was immunomodulatory as gene expression and flow cytometric analysis revealed significantly decreased in immune cell infiltration, synthesis of ROS, inflammatory chemokines, cytokines, CD8 T cell effector responses, and concomitant increases in alternatively-activated M2 macrophage and dendritic cell phenotypes. Our results provide evidence that reducing oxidative stress following allotransplantation of (PVPON/TA)-encapsulated islets can elicit localized immunosuppression and potentially delay graft destruction in future human islet transplantation studies.