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Winau, Florian

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Winau

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Florian

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Winau, Florian
Author's Publications: search.filters.isAuthorOfPublication.8ebfc85d-302a-4ea3-9223-b81e6d838800

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Now showing 1 - 4 of 4
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    CD1a on Langerhans cells controls inflammatory skin diseases
    (2016) Kim, Ji Hyung; Hu, Yu; Yongqing, Tang; Kim, Jessica; Hughes, Victoria A.; Nours, Jérôme Le; Marquez, Elsa A.; Purcell, Anthony W.; Wan, Qi; Sugita, Masahiko; Rossjohn, Jamie; Winau, Florian
    CD1a is a lipid-presenting molecule abundantly expressed on Langerhans cells. However, the in vivo role of CD1a remains unclear, principally because CD1a is lacking in mice. Using CD1a-transgenic mice, we show that the plant-derived lipid urushiol triggers CD1a-dependent skin inflammation, driven by CD4+ T cells producing IL-17 and IL-22. Human subjects with poison ivy dermatitis showed a similar cytokine signature following CD1a-mediated urushiol recognition. Among different urushiol congeners, we identified diunsaturated pentadecylcatechol (C15:2) as the dominant antigen for CD1a-restricted T cells. We determined the crystal structure of the CD1a-urushiol (C15:2) complex, demonstrating the molecular basis of urushiol interaction with the antigen-binding cleft of CD1a. In a mouse model and psoriasis patients, CD1a amplified inflammatory responses mediated by TH17 cells reactive with self lipid antigens. Treatment with blocking antibodies against CD1a alleviated skin inflammation. Thus, we propose CD1a as a potential therapeutic target in inflammatory skin diseases.
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    Scramblase TMEM16F terminates T cell receptor signaling to restrict T cell exhaustion
    (The Rockefeller University Press, 2016) Hu, Yu; Kim, Ji Hyung; He, Kangmin; Wan, Qi; Kim, Jessica; Flach, Melanie; Kirchhausen, Tom; Vortkamp, Andrea; Winau, Florian
    In chronic infection, T cells become hyporesponsive to antigenic stimulation to prevent immunopathology. Here, we show that TMEM16F is required to curb excessive T cell responses in chronic infection with virus. TMEM16F-deficient T cells are hyperactivated during the early phase of infection, exhibiting increased proliferation and cytokine production. Interestingly, this overactivation ultimately leads to severe T cell exhaustion and the inability of the host to control viral burden. Mechanistically, we identify TMEM16F as the dominant lipid scramblase in T lymphocytes that transports phospholipids across membranes. TMEM16F is located in late endosomes, where it facilitates the generation of multivesicular bodies for TCR degradation and signal termination. Consequently, TMEM16F deficiency results in sustained signaling and augmented T cell activation. Our results demonstrate that scramblase restricts TCR responses to avoid overactivation, ensuring a well-balanced immune response in chronic infectious disease.
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    The histone demethylase UTX regulates the lineage-specific epigenetic program of invariant natural killer T cells
    (Springer Nature, 2016) Beyaz, Semir; Kim, Ji Hyung; Pinello, Luca; Xifaras, Michael E; Hu, Yu; Huang, Jialiang; Kerenyi, Marc A; Das, Partha Pratim; Barnitz, R Anthony; Herault, Aurelie; Dogum, Rizkullah; Haining, William; Yilmaz, Omer; Passegue, Emmanuelle; Yuan, Guo-Cheng; Orkin, Stuart; Winau, Florian
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    Natural Killer T Cells Activated by a Lipopeptidophosphoglycan from Entamoeba histolytica Are Critically Important To Control Amebic Liver Abscess
    (Public Library of Science, 2009) Lotter, Hannelore; González-Roldán, Nestor; Lindner, Buko; Winau, Florian; Isibasi, Armando; Moreno-Lafont, Martha; Ulmer, Artur J.; Holst, Otto; Tannich, Egbert; Jacobs, Thomas
    The innate immune response is supposed to play an essential role in the control of amebic liver abscess (ALA), a severe form of invasive amoebiasis due to infection with the protozoan parasite Entamoeba histolytica. In a mouse model for the disease, we previously demonstrated that Jα18-/- mice, lacking invariant natural killer T (iNKT) cells, suffer from more severe abscess development. Here we show that the specific activation of iNKT cells using α-galactosylceramide (α-GalCer) induces a significant reduction in the sizes of ALA lesions, whereas CD1d−/− mice develop more severe abscesses. We identified a lipopeptidophosphoglycan from E. histolytica membranes (EhLPPG) as a possible natural NKT cell ligand and show that the purified phosphoinositol (PI) moiety of this molecule induces protective IFN-γ but not IL-4 production in NKT cells. The main component of EhLPPG responsible for NKT cell activation is a diacylated PI, (1-O-[(28∶0)-lyso-glycero-3-phosphatidyl-]2-O-(C16:0)-Ins). IFN-γ production by NKT cells requires the presence of CD1d and simultaneously TLR receptor signalling through MyD88 and secretion of IL-12. Similar to α-GalCer application, EhLPPG treatment significantly reduces the severity of ALA in ameba-infected mice. Our results suggest that EhLPPG is an amebic molecule that is important for the limitation of ALA development and may explain why the majority of E. histolytica-infected individuals do not develop amebic liver abscess.