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• W3088173614 abstract "Designing an adjuvant that induces mucosal as well systemic immunity has been long desired. Mucosal vaccines are more effective in combating respiratory pathogens as they induce specific IgA and mucosal T cell responses. However, developing mucosal adjuvants is very challenging due to nature of the mucosal barrier environment. In our previous studies we have shown that our intranasal adjuvant (oil-in-water based nanoemulsion-NE) interacts with epithelial cells and induces dendritic cell-specific retinaldehyde dehydrogenase (RALDH) activity in immunized animals. RALDH converts vitamin A into retinoic acid (RA), orchestrating T cell homing towards the mucosal sites as well as IgA production. We now seek to evaluate the signaling that underlies this RALDH activation. To examine the efficacy of NE in-vitro, we simulated in-vivo intranasal immunization in a co-culture model. We treated the epithelial cells with different formulations of NE, followed by co-culturing with dendritic and T cells. Further, animals were intranasally immunized with ova-albumin (Ova) in combination to NE (with and without RA) to study RALDH production by mucosal DCs, T cell gut homing, IgA production and Th1/ Th17 cytokine production. NE induced RALDH activity in co-cultured DCs and induced gut homing marker expression on T cells in-vitro. Also, immunization with NE-Ova showed increased RALDH activity in DCs, even in the absence of RA, resulting in increased ova-specific IgA production as well as T cell gut homing. Furthermore, antibody titers and cytokine data suggested and increased Th1/Th17 response while a suppression of Th2. In-vitro studies showed NE activates RALDH via MyD88 pathway and utilizes p65 signaling in DCs. Of interest, signaling did not go through TLR2 or 4, and was maintained in animals who lack RA in their dendritic cells. NE activated RALDH activity in DCs via MyD88 and p65 signaling and enhanced mucosal immune responses in gut associated lymphoid tissues. These results suggest a unique mechanism of activation of RALDH by this adjuvant." @default.
• W3088173614 created "2020-10-01" @default.
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• W3088173614 date "2020-08-01" @default.
• W3088173614 modified "2023-09-26" @default.
• W3088173614 title "Intranasal adjuvant induces retinaldehyde dehydrogenase activity in dendritic cells via p65 signaling" @default.
• W3088173614 doi "https://doi.org/10.1016/j.waojou.2020.100339" @default.
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