To be able to study the cellular interactions and mechanisms proposed, we have generated a new panel of tools: new specific NPs interacting with the desired T and B lymphocytes, new tools to be able to detect them, as well as new mouse strains that will afford us to investigate the desired cell populations. Although we have encountered some challenges to generate these tools, specially the new specific NPs, they have all been successfully generated. Using these new tools as well as others previously generated in the host laboratory, we have been able to generate specific TR1 cells, the cell type responsible for the restoration of normoglycemia in T1D mice, the main focus of this study. Using a technique called RNA-sequencing, we have been able to characterize them much further than ever before, confirming some previous results and uncovering new, very interesting molecules that are specific to this population. New experiments to further characterize these cells are currently on course. A similar study with specific Breg cells (the other main target of this study) will be done soon to complete the study. Yet, to characterize the role of B cells in NP treatments we have used a relevant, B cell dependent autoimmune disease: pemphigus vulgaris. Using a mouse model for this disease we have been able to reduce the levels of auto-antibodies in serum of mice treated with our specific NPs, showing that TR1 cells generated by the inoculated NPs are able to regulate antibody producing B cells.
Finally, we have used a model of humanized mice to test our specific NP treatments on human lymphocytes obtained from T1D donnors. We have been able to detect an increase in regulatory B cells that correlates with the upregulation of TR1 cells.
These results will afford the host lab to better understand the intrinsic mechanisms of this new therapy based on coated NPs, therefore increasing the chances of generating better treatments for a wider array of autoimmune diseases. Once these results are completed with the final experiments that are now on course, at least one scientific paper will be published in a high impact, open-access journal.
This project and results have also been disclosed to the scientific public in one national and one international Congresses, and to the general public in several talks given at cultural centers, schools and a science museum.
