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Hang, Saiyu

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Hang

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Saiyu

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Hang, Saiyu

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2013 - 20182

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Author's Publications: search.filters.isAuthorOfPublication.54bc664e-ce1d-4aa1-ac97-f16808691943

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    Mutations in the IMD Pathway and Mustard Counter Vibrio cholerae Suppression of Intestinal Stem Cell Division in Drosophila
    (American Society of Microbiology, 2013) Wang, Zhipeng; Hang, Saiyu; Purdy, Alexandra E.; Watnick, Paula
    ABSTRACT Vibrio cholerae is an estuarine bacterium and an intestinal pathogen of humans that causes severe epidemic diarrhea. In the absence of adequate mammalian models in which to study the interaction of V. cholerae with the host intestinal innate immune system, we have implemented Drosophila melanogaster as a surrogate host. We previously showed that immune deficiency pathway loss-of-function and mustard gain-of-function mutants are less susceptible to V. cholerae infection. We find that although the overall burden of intestinal bacteria is not significantly different from that of control flies, intestinal stem cell (ISC) division is increased in these mutants. This led us to examine the effect of V. cholerae on ISC division. We report that V. cholerae infection and cholera toxin decrease ISC division. Because IMD pathway and Mustard mutants, which are resistant to V. cholerae, maintain higher levels of ISC division during V. cholerae infection, we hypothesize that suppression of ISC division is a virulence strategy of V. cholerae and that accelerated epithelial regeneration protects the host against V. cholerae. Extension of these findings to mammals awaits the development of an adequate experimental model.
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    Bile Acid Metabolites Control Th17 and Treg Cell Differentiation
    (Cold Spring Harbor Laboratory, 2018-11-08) Huh, Jun; Hang, Saiyu; Paik, Donggi; Yao, Lina; Kim, Eunha; Trinath, Jamma; Lu, Jingping; Ha, Soyoung; Nelson, Brandon; Kelly, Samantha; Wu, Lin; Zheng, Ye; Longman, Randy; Rastinejad, Fraydoon; Devlin, A. Sloan; Krout, Michael; Fischbach, Michael; Littman, Dan
    Bile acids are abundantly present in the mammalian gut, where they undergo bacteria-mediated transformation, generating a large pool of bioactive molecules. While they have been shown to affect host metabolism, cancer progression and innate immunity, it is unknown whether bile acids affect the function of adaptive immune cells such as T cells expressing IL-17a (Th17 cells) and regulatory T cells (Tregs) that mediate inflammatory and anti-inflammatory responses, respectively. By screening a small-molecule library primarily composed of bile acid metabolites, we identified two distinct derivatives of lithocholic acid (LCA), 3-oxoLCA and isoalloLCA, as specific regulators of Th17 and Treg cells. While 3-oxoLCA inhibited Th17 cell differentiation by directly binding to its key transcription factor RORγt (retinoid-related orphan receptor γ t), isoalloLCA enhanced differentiation of Tregs through mitochondrial-dependent metabolic changes, leading to an increased expression of Foxp3. IsoalloLCA-dependent Treg enhancement required an intronic Foxp3 enhancer, the conserved noncoding sequence 3 (CNS3), which acts as an epigenetic switch that confers a poised state to the Foxp3 promoter. Lastly, oral administration of 3-oxoLCA and isoalloLCA to mice led to reduced Th17 and increased Treg cell differentiation in the intestinal lamina propria. Altogether, our data suggest novel mechanisms by which bile acid metabolites control host immune responses by directly modulating the Th17 and Treg balance.