Engineered Human Dendritic Cell Exosomes as Effective Delivery System for Immune Modulation

Exosomes (exos) contain molecular cargo of therapeutic and diagnostic value for cancers other inflammatory diseases, but their potential periodontitis (PD) remains unclear. Dendritic cells (DCs) are the directors immune response have been extensively used in therapy. We previously reported a mouse model PD that custom murine DC-derived exo subtypes could reprogram toward bone-sparing or bone-loss phenotype, depending on profile. Further advancement this technology requires testing human DC-based exos with target cells. Our main objective study is to test hypothesis monocyte-derived dendritic cell (MoDC)-derived constitute well-tolerated effective approach modulate DC T responses vitro. MoDC were generated TGFb/IL-10 (regulatory (reg) MoDCs, CD86lowHLA-DRlowPDL1high), E. coli LPS (stimulatory (stim) CD86highHLA-DRhighPDL1low) buffer (immature (i) CD86lowHLA-DRmedPDL1low). isolated from different characterized. Once released secreting into surrounding environment, exosomes protect prepackaged deliver it bystander This modulates functions these cells, content. RegMoDCexos internalized by recipient MoDCs induced upregulation PDL1 downregulation costimulatory molecules CD86, HLADR, CD80, while stimMoDCexos had opposite influence. CD25+Foxp3+ Tregs, which expressed CTLA4 PD1 not IL-17A. In contrast, treated IL-17A+ Th17 negative immunoregulatory PD1. DCs iMoDCexos ‘neutral’, equivalent controls. conclusion, present an delivery system Thus, may viable immunotherapeutic agent modulating gingival tissue inhibit bone loss periodontal disease.