Tu132 - Anti-inflammatory NKT Cell Activation Induces Expansion of Regulatory B Cells That Ameliorates Inflammation

Constanza Zurita – Instituto de Ciencias Biomédicas – Millennium Institute on Immunology and Immunotherapy, Universidad de Chile; Richard García-Betancourt – PhD, Instituto de Ciencias Biomédicas, Millennium Institute on Immunology and Immunotherapy, Universidad de Chile; Pablo Palacios – PhD(c), Instituto de Ciencias Biomédicas, Millennium Institute on Immunology and Immunotherapy, Universidad de Chile; Fernanda Aguirre-Muñoz – Instituto de Ciencias Biomédicas – Millennium Institute on Immunology and Immunotherapy, Universidad de Chile; Enzo Jiménez-Oliva – Instituto de Ciencias Biomédicas – Millennium Institute on Immunology and Immunotherapy, Universidad de Chile; Leandro Carreño, PhD – Associate Professor and Deputy Director, Instituto de Ciencias Biomédicas, 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 its differentiation 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 liposomes, in order to both activate iNKT cells and modulate the immune response in an antigen-specific manner on an OVA-specific inflammatory model.
Mice were treated intranasally with liposomal formulations, in order to evaluate the recruitment and expansion of regulatory immune cells given the activation of iNKT cells. Physicochemical and functional characterization of the formulations were assessed previous to the administration. Characterization of the immune cell population on pulmonary tissue was assessed through flow cytometry after treatment. Histopathologic characteristics of pulmonary tissue was also evaluated.
In vivo, we found that the immunization of glycolipid-containing liposomes led to the expansion, activation and production of cytokines from iNKT cells. Activation of iNKT cells led to the expansion of both regulatory T and B cells. Additionally, the production of IL-10 was enhanced in the aforementioned cells. The administration of the liposomal formulation alleviated the pulmonary inflammatory response, reducing the production of mucus, goblet cell hyperplasia and leukocyte infiltration.
Herein, we present a novel strategy to alleviate the inflammatory response through the expansion regulatory cells given by the activation of iNKT cells, becoming the first step to generate a cutting-edge strategy to reduce inflammatory disorders.