Hat RF + EVs are involved in RA pathogenesis.PT09.Extracellular vesicles (EVs) secreted by mesenchymal stem cells (MSCs) exert opposite effects with respect to their cells of origin in mice with DSS-induced colitis Michele Grassi1; Martina Piccoli1; Anna Maria Tolomeo1; Chiara Franzin2; Marcin Jurga3; Barbara Lukomska4; Chiara Marchiori1; Andrea Porzionato1; BRPF3 Inhibitor medchemexpress Ignazio Castagliuolo1; Michela Pozzobon2; Maurizio MuracaThursday, 03 May1 University of Padova, Italy, Padova, Italy; 2Stem Cells and Regenerative Medicine Lab, Fondazione Istituto di Ricerca Pediatrica Cittdella Speranza, Padova, Italy; 3The Cell Factory BVBA (Esperite NV), Niel, Belgium; 4NeuroRepair Department, MMRC, PAS, Warsaw, PolandBackground: Several reports have described a helpful impact of MSC administration in mice with experimental colitis. On the other hand, worsening of colitis following MSC therapy was also reported. Methods: We compared the effects of MSCs or MSC-EV administration in dextran sulfate sodium (DSS) colitis model. Because cytokine conditioning was reported to enhance MSC immune modulatory activity, the cells were kept either below typical culture situations (na e, nMSCs) or primed by IL1b, IL6 and TNFalfa (induced, iMSCs) Colitis was induced in C57BL/6 mice with DSS in drinking water for 5 days followed by two days on plain water. Healthier EP Modulator supplier controls received plain water. Colitic animals have been assigned to one of the following remedies on days 3, 5 and 7: car only (controls), 1 107 nMSCs, 1 107 iMSCs, three 1010 nMSC-EVs and three 1010 iMSC-EVs. Animals had been sacrificed on day 8. To assess colitis severity we determined: changes in physique wt, Disease Activity Index, colon length, histomorphometric analysis in the entire colon, cytokine expression in intestinal mucosa. Results: nMSCs and iMSCs administration was related with clinical and histological worsening with respect to controls. Having said that, mice treated with each nMSC-EVs and iMSC-EVs showed clinical improvement, even when no considerable distinction was discovered in histological/morphometric score with respect to controls. These opposite effects have been particularly evident with iMSCs. Cytokine expression in colon mucosa showed lowered TNFalpha and increased IL-10 in mice treated with iMSC-EVs. Summary/Conclusion: In conclusion, each nMSCs and iMSCs worsened DSS-induced colitis, confirming that these cells can behave as pro-inflammatory agents depending on the environment. In contrast, both nMSC-EVs and iMSC-EVs showed a partially useful effect, suggesting a additional predictable behaviour as well as a safer therapeutic profile with respect to their cells of origin. Funding: The BROAD Healthcare Analysis Plan AT CCFA supported this workthat the proportion of OLFM4-positive neutrophils was shown to become higher in individuals with progressive GPP than that in controls. Summary/Conclusion: Taken with each other, these information recommend that neutrophil-derived exosomes enter keratinocytes to stimulate the expression and secretion of CXCLs, IL36G and TNF, resulting in the chemotaxis of more neutrophils, which promotes the autoinflammatory responses in generalized pustular psoriasis. Funding: This perform was supported by National Organic Science Foundation of China [nos. 81430073 and 81502716]PT09.Pro-inflammatory function of blister fluid-derived exosomes in bullous pemphigoid Hui Fang; Shuai Shao; Man Jiang; Gang Wang Department of Dermatology, Xijing Hospital, Fourth Military Health-related University, Xi’an, China (People’s Republic)PT09.Neutrophil-derived exosome.
