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- W4313373596 abstract "Abstract Fibroblastic reticular cells (FRCs) provide critical regulation of T and B cell. Our recent study shown metabolic reprogramming through Interleukin 17 (IL-17) was critical for the FRCs expansion and autoantibody production. Although studies shown IL-17 is important for B-cell activation and induction of IgA responses, the mechanisms have been unclear. We further hypothesized IL-17 signaling in FRCs is critical to drive protective antibody responses, and prior FRCs activation through a distinct inflammatory episode could enhance this response. We employed Dextran Sulfate Sodium (DSS) induced-colitis followed by Citrobacter rodentium infection model. Mice pretreated with DSS shown increased FRCs expansion and germinal center (GC) formation and enhanced anti-Citrobacter antibody production, leading to a quicker Citrobacter clearance, less colon inflammation and better outcome. IL17a neutralization in DSS phase blocked both the expansion of FRCs and the enhanced B cell response. We further confirmed FRCs failed to expand during Citrobacter infection in FRC-restricted IL-17RA deletion mice. These mice had reduced antibody production in both serum and feces, along with higher Citrobacter burden. We previously shown IL-17 induction IκB-ζ was required for metabolic reprogramming in vitro. Now, we found FRC-intrinsic IκB-ζ expression was required for in vivo Cpt1a (a rate-limiting transporter for fatty acid oxidation) expression, GC formation and antibody responses. RNAseq data suggest GC survival factors such as IL-6 and BAFF were increased by IL-17 signaling in FRCs. In conclusion, IL-17 indirectly promotes GC formation and antibody responses by inducing IκB-ζ expression in activated LN stromal cells during gut infection." @default.
- W4313373596 created "2023-01-06" @default.
- W4313373596 creator A5026972754 @default.
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- W4313373596 date "2020-05-01" @default.
- W4313373596 modified "2023-09-27" @default.
- W4313373596 title "IL-17 promotes protective antibody during gut infection through IκB-ζ-dependent LN stromal cell activation" @default.
- W4313373596 doi "https://doi.org/10.4049/jimmunol.204.supp.60.13" @default.
- W4313373596 hasPublicationYear "2020" @default.
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