Harnessing Nanoparticle Technology for Celiac Disease: A Path to Immune Tolerance

The study explores a potential treatment for celiac disease by focusing on the restoration of T-cell tolerance to a protein called gliadin. Researchers examined the impact of using negatively charged nanoparticles made of poly(lactide-co-glycolide), which encapsulate the gliadin protein (referred to as TIMP-GLIA), on three different mouse models of the disease. These nanoparticles have previously shown to induce immune tolerance in other autoimmune conditions.

The experimental methods included the use of various mouse models, such as C57BL/6, RAG1-deficient, and HLA-DQ8 transgenic mice. The mice received tail-vein injections of either TIMP-GLIA or control nanoparticles. Some were also subjected to immunization and ear challenge procedures using gliadin and other proteins. In addition, RAG-deficient mice were given T cells from gliadin-immunized mice and were fed a diet containing wheat gluten. Various assays, including proliferation and cytokine secretion tests, flow cytometry, RNA sequencing, and real-time quantitative PCR, were used to analyze the cells and tissues. Serum samples were tested for gliadin antibodies, and intestinal tissues were examined histologically.

The results indicated that TIMP-GLIA did not trigger maturation in cultured human dendritic cells or activate T cells from celiac disease patients. In the three mouse models, TIMP-GLIA injections significantly reduced gliadin-specific T-cell proliferation, inflammatory cytokine release, gliadin-specific antibodies, ear swelling, gluten-dependent enteropathy, and body weight loss. The effects were found to be dose-dependent in one of the models. Furthermore, the spleen cells from mice that received TIMP-GLIA nanoparticles exhibited increased levels of FOXP3 and gene expression indicative of tolerance induction.

The conclusion drawn from the study suggests that TIMP-GLIA nanoparticles can induce a state of unresponsiveness to gliadin and decrease inflammation and enteropathy markers in mice with gliadin sensitivity. This approach could potentially be developed into a treatment for celiac disease.