WCN26-8197 BUDESONIDE MODULATES B- AND T-CELL IMMUNITY IN PEYER'S PATCHES: IMPLICATIONS FOR IgA NEPHROPATHY

transduction which primarily targets liver cells.Unexpectedly, despite successful restoration of plasma FD, AP complement activity was not recovered in the treated mice.Further investigation showed that plasma FB was mostly missing in the AAV8/mature FD-treated FD KO mice.Similar FB depletion also occurred in wild-type but not C3 KO mice after AAV8/mature FD treatment.Conversely, depletion of FB was not observed in mice treated with AAV8/pro-FD gene transduction or in mice with ectopic expression of mature FD in bone marrow/blood cells via retrovirus-mediated gene transduction.When Hepa1-6 cells were induced to express C3, FB and mature FD, intact FB was lost from the culture supernatant.Vemircopan was able to prevent FB depletion, unlike FD monoclonal antibody.Finally, the depletion of FB by AAV8/mature FD effectively prevented the development of disease in murine models of atypical hemolytic uremic syndrome and C3 glomerulopathy.Conclusion: Our data suggest that the regulation of FD by MASP3 and the segregated biosynthesis of FD, FB and C3 have physiological significance.The ectopic expression of mature FD in the liver causes C3dependent FB depletion, a phenomenon that could be exploited for the treatment of complement-mediated AP diseases.I have no potential conflict of interest to disclose.I did not use generative AI and AI-assisted technologies in the writing process.