Biomimetic immunomodulation by crosstalk with nanoparticulate regulatory T cells

Hyperactive immunity mediates the development and progression of various immuno-inflammatory diseases. However, the use of immunosuppressive or anti-inflammatory agents has been largely restricted either by off-target side effects or by individual interaction site. Here, we describe a biomimetic manipulation strategy for immunosuppression by crosstalk with regulatory T (Treg) cell membrane-coated nanoparticles. Due to the reservation of intrinsic membrane proteins and function from Treg cells, coated nanoparticles can directly interact with multifaceted overactive immune cells. By virtue of this unique characteristic, nanoparticulate Treg cells inhibit macrophage-osteoclast differentiation, the maturation of dendritic cells, and the activation of effector T cells. In both murine and canine models of periodontitis, these nanoparticles successfully suppress excessive immune responses, alleviating inflammation and curbing alveolar bone resorption. Our work reveals how dysregulated immune responses can be effectively manipulated by biomimetic immunomodulation and proposes the utilization of nanoparticulate Treg cells as a promising approach to treat immuno-inflammatory diseases.