S (CD69) and heavily skewed T-cells towards TH1/TH17 responses. T-bet and RORgamma-T had been substantially enhanced, as was production of IL-2 and IL-17A expression. IL-4 and IL-13 production were unchanged or slightly but non-significantly decreased, and GATA-3 expression was unaffected. Adjustments in NF-kappaB expression were variable and did not attain significance. Dose dependence of all constructive benefits was observed. Summary/conclusion: EVs from cells exposed most straight to cigarette smoke and its by-products may transmit inflammatory signals to other cells by way of EVs. We are presently investigating this phenomenon inside the context of HIV infection and disease. Funding: This analysis was supported in element by the US National Institutes of Overall health by means of DA040385 (to KWW, MO, and CT).Thursday, 03 MayOT02.Mesenchymal stromal cell extracellular vesicles modulate innate and adaptive immune cells at multi-organ level in a model of bronchopulmonary dysplasia Monica Reis1; Gareth R. Jagged-1/CD339 Proteins custom synthesis Willis2; Complement Factor P Proteins Purity & Documentation Angeles Fernandez-Gonzalez2; Nahal Mansouri2; Alex Mitsialis2; Stella Kourembanas2 Division of Pediatrics, Harvard Medical College, Boston, Massachusetts, USA, Boston, USA; 2Division of Newborn Medicine Division of Medicine, Boston Children’s Hospital, Boston, Massachusetts, USABackground: Bronchopulmonary dysplasia (BPD) is a multifactorial chronic disease that happens predominantly in preterm infants receiving oxygen therapy and mechanical ventilation, and is characterized by lung development arrest, diminished alveolar and blood vessel improvement and impaired pulmonary function. Making use of a murine model in hyperoxia-induced BPD, we lately showed that a bolus dose of MSC extracellular vesicles (MEx) enhanced lung architecture and lung function and that this therapeutic impact was connected with modulation of lung macrophage phenotypes. Having said that, BPD is a disease with multi-organ effects. Thus, we extend our research within this BPD model to investigate the immunomodulatory effects of MEx around the innate and adaptive immune responses in the multiorgan level. Solutions: Extracellular vesicles were collected from the conditioned media of human Wharton’s Jelly-MSCs and purified by means of density flotation in Iodixanol. Newborn mice were exposed to hyperoxia on postnatal day 1 (PN1) (75 O2), treated with MEx on PN4 and returned to space air on PN7. Treated animals and suitable controls have been harvested on PN7 and PN14 for histologic and cytometric assessment of lungs, spleen and thymus. Benefits: Hyperoxia-exposed mice presented important lung harm and alveolar simplification as well as medullary involution in the thymus. Injection of MEx into hyperoxic-mice improved lung histology and restored thymic cortico-medullary ratios to levels akin to their normoxic counterparts. At PN7, MEx treatment modulated macrophages into an anti-inflammatory phenotype and mobilized inflammatory LY6ChiCCR2+ monocytes within the lungs and spleens. At PN14, MEx remedy induced a multi-organ reduction of inflammatory monocytes with a shift to a regulatory phenotype. Particularly, MEx altered T-cell subpopulation levels, inducing a reduction in CD8+ lymphocytes and a rise in CD4+ lymphocytes, and promoting the generation of CD4 +CD25hiFoxP3+ regulatory T cells. Summary/conclusion: Applying a hyperoxia-induced BPD model, we show that MSC extracellular vesicle therapy benefits inside a profound multiorgan effect around the immune system and promotes a tolerogenic T-cell phenotype that plays a essential rol.