Nanoparticle-enabled CD40 silencing programs immune tolerance via a DC-Treg-Breg axis in autoimmune myocarditis

regulatory T cells and IL-10-producing regulatory B cells, together with suppression of pathogenic Th17 responses. Functionally, siCD40/NP treatment attenuated myocardial inflammation, limited chronic fibrotic remodeling, and preserved ventricular function without evidence of overt systemic toxicity. Notably, regulatory B cells were enriched in cardiac-draining lymphoid tissues during the chronic phase, suggesting a spatially organized tolerance mechanism that contributes to durable disease control. Collectively, these findings identify nanoparticle-enabled CD40 silencing as a materials-based strategy for immune tolerance programming and highlight antigen-presenting cell reprogramming as a promising design principle for immunoregulatory biomaterials in inflammatory heart disease.