Immunomodulation of Dendritic Cells Using Tannic Acid-Based Capsules

Abstract

In type 1 diabetes (T1D), insulin-secreting β-cells are destroyed by autoreactive immune cells, for which tolerance to β-cell antigens is lost. Dendritic cells (DC) are potent antigen-presenting cells in the activation of autoreactive T cells during T1D progression. Activation of naïve CD4 T cells relies on three signals: 1.) binding of the T cell receptor with processed antigenic peptides presented by MHC-II complex, 2.) co-stimulatory molecule interactions, and 3.) synthesis of pro-inflammatory cytokines and reactive oxygen species. We previously demonstrated that dissipation of this third signal impairs autoreactive T cell activation. In this study, we tested the hypothesis that encapsulation of putative T1D autoantigens with an antioxidant-containing biomaterial would induce immune tolerance, following phagocytosis by activated DC. We generated bone marrow-derived DC and co-cultured these cells with LPS and microcapsules comprised of a neutral polymer and multilayers of tannic acid (TA), a known antioxidant. Induction of a tolerogenic DC phenotype was assessed by expression of pro-inflammatory cytokine mRNA by qPCR and secretion of cytokines by ELISA. Our data show that a subgroup of TA-based microcapsules can blunt DC responses, as shown by a significant decrease in mRNA accumulation of the pro-inflammatory cytokines Tnfa (p ≤ 0.01) and Il12b (p ≤ 0.01), as well as the chemokine Cxcl10 (p ≤ 0.01). We also observed a significant decrease in secreted IL-12p70 as measured by ELISA. Future studies will encapsulate autoantigens such as insulin and following phagocytosis, determine if a tolerogenic DC phenotype can abrogate autoreactive T cell responses. Disclosure J. Feduska: None. H.M. Tse: None.