Objectif The complexity of autoimmune responses is a barrier to the design of strategies that can selectively purge the immune system of autoreactivity without impairing systemic immunity. Recently, Santamaria et al. have shown that nanoparticles (NPs) coated with type 1 diabetes (T1D)-relevant peptide–MHC (pMHC) complexes can restore normoglycemia in diabetic animals by blunting the diabetogenic autoimmune response without impairing systemic immunity. pMHC class II-NP therapy functions by expanding, in an epitope-specific manner, autoantigen-experienced T-regulatory-1 (TR1) CD4+ T-cells that inhibit the recruitment of other autoantigenic specificities by: (1) suppressing autoantigen-loaded antigen-presenting cells in the pancreatic lymph nodes (PLNs); and (2) promoting the differentiation of B-cells into B-regulatory cells. Importantly, they have shown that human T1D-relevant pMHC class II-NPs also promote human TR1 CD4+ T-cell formation in NSG mice engrafted with peripheral blood mononuclear cells from recent onset T1D patients. Here, I propose a multidisciplinary approach to test the following hypotheses: (1) Breg formation is driven by a cognate interaction between TR1 cells and autoreactive B-cells; (2) TR1-derived cytokines play critical roles in TR1-driven Breg conversion in vivo; and (3) the B-cells that are recruited to the PLNs of pMHC-NP-treated humanized NSG mice are enriched for Breg cells. Furthermore, I will work with the enterprise SEPMAG, to design a scalable magnetic separation device for future clinical development of these compounds.Collectively, NANOBreg will provide new insights into the biology of the TR1-Breg regulatory pathway and will enhance our knowledge on the mechanisms of action of this novel therapeutic approach. In addition, it will address a manufacturing bottleneck by bridging academic research with the manufacturing industry while enhancing my career development in an area of huge potential growth and translational significance. Champ scientifique medical and health sciencesclinical medicineendocrinologydiabetesengineering and technologyelectrical engineering, electronic engineering, information engineeringinformation engineeringtelecommunicationstelecommunications networksmobile networkmedical and health sciencesmedical biotechnologynanomedicinemedical and health sciencesbasic medicineimmunologyautoimmune diseasesengineering and technologynanotechnologynano-materials Mots‑clés Autoimmunity Type 1 Diabetes Nanomedicine Nanoparticles Peptide-Major Histocompatibility Complexes Regulatory T-cells Regulatory B-cells Transgenic Mice Lineage Tracing Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Thème(s) MSCA-IF-2015-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF) Appel à propositions H2020-MSCA-IF-2015 Voir d’autres projets de cet appel Régime de financement MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF) Coordinateur FUNDACIO DE RECERCA CLINIC BARCELONA-INSTITUT D INVESTIGACIONS BIOMEDIQUES AUGUST PI I SUNYER Contribution nette de l'UE € 158 121,60 Adresse CARRER ROSSELLO 149 08036 Barcelona Espagne Voir sur la carte Région Este Cataluña Barcelona Type d’activité Research Organisations Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 158 121,60