Project Abstract Periodontitis (PD) is a bone degenerative inflammatory disease that contributes to increased risk of other diseases with more serious mortality and morbidity profiles. We propose here a novel immune therapeutic strategy for PD, using cellular nano-particles, exosomes (EXO) from dendritic cells. Dendritic cells are the “directors” of the adaptive immune response, as such, their immune functions can be exploited to treat chronic immune-mediated diseases such as cancer and autoimmune diseases. This is first study to our knowledge to employ phenotypically stable exosomes from dendritic cells to treat experimental PD in mice. Our strategy consists of “reprograming” immune cells in the periodontium responsible for destructive inflammatory bone loss using custom DC exo. Our tactic is to inject DC exo directly into the gingiva, to target anti-inflammatory pathways in specific immune cells, to prevent/resolve alveolar bone loss. The overall objective of these studies to acquire a better understanding of the immunobiology of DC-derived exo in vivo and in vitro in the murine model of experimental PD, and relate these findings to exo isolated from humans with PD. Our aims are to test the hypotheses that: Aim 1. Exogenous DCexo delivered to the PD lesion persist in situ and reprogram recipient DCs and T cells involved in experimental PD in mice in vivo; Aim 2. DC exo preserve molecular cargo and reprogram acceptor DCs and T cells through receptor binding and endocytosis; Aim 3. Endogenous exo from humans with PD contain molecular cargo of direct relevance to exo therapy and PD pathogenesis. Future goals include: 1. the development of DC exo therapy for PD in humans, 2. assessment of salivary exo molecular cargo for diagnostic potential in PD and other oral diseases