W140 - Invariant Natural Killer T Cells Activation by a Novel Glycolipid-containing Nanoparticle Formulation Induces Expansion of Regulatory Immune Cells

Richard García-Betancourt, PhD – Millennium Institute on Immunology and Immunotherapy, Universidad de Chile; Pablo Palacios, PhD(c) – Millennium Institute on Immunology and Immunotherapy, Universidad de Chile; Álvaro Santibañez, PhD – Millennium Institute on Immunology and Immunotherapy, Universidad de Chile; Leandro Carreño, PhD – Associate Professor, Millennium Institute on Immunology and Immunotherapy, Universidad de Chile

Abstract Text: Invariant Natural Killer T (iNKT) cells are characterized by its capacity to secrete diverse cytokines after its activation. Such cytokines can modulate the function of multiple immune cells, including the differentiation of diverse immune cells towards a regulatory profile, which enables these cells to modulate the immune response and restore the immunological tolerance.
Here, we incorporated iNKT cells-activating glycolipids and ovalbumin (OVA) into liposomal nanoparticles, in order to both activate iNKT cells and modulate the immune response in an antigen-specific manner.
Liposomes were generated by thin lipid film hydration and extrusion, following OVA-anchoring to its surface. Physicochemical and functional characterization of the different liposomal formulations were assessed previous to the administration of the nanoparticles in OVA-sensitized mice. In vivo, we found that the immunization of glycolipid-containing liposomes led to the expansion, activation and production of a specific cytokines profile from iNKT cells. Furthermore, activation of iNKT cells led to significant expansion of regulatory B (Bregs), regulatory T (Tregs) and type 1 regulatory T (Tr1) cells. Additionally, the production of anti-inflammatory cytokine IL-10 was enhanced in the aforementioned cells, given by the activity of iNKT cells.
Herein, we present a novel strategy to expand regulatory cells given by the activation of iNKT cells, induced by different nanoparticle formulations, becoming the first step to generate a cutting-edge strategy to reduce the inflammatory response and reestablish immunotolerance on different types of pathologies.