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Piepke, Marius; Clausen, Bettina H.; Ludewig, Peter; Vienhues, Jonas H.; Bedke, Tanja; Javidi, Ehsan; Rissiek, Björn; Jank, Larissa; Brockmann, Leonie; Sandrock, Inga; Degenhardt, Karoline; Jander, Alina; Roth, Vanessa; Schädlich, Ines S.; Prinz, Immo; Flavell, Richard A.; Kobayashi, Yasushi; Renné, Thomas; Gerloff, Christian; Huber, Samuel; Magnus, Tim; Gelderblom, Mathias

Interleukin-10 improves stroke outcome by controlling the detrimental Interleukin-17A response

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  • Medientyp: E-Artikel
  • Titel: Interleukin-10 improves stroke outcome by controlling the detrimental Interleukin-17A response
  • Beteiligte: Piepke, Marius; Clausen, Bettina H.; Ludewig, Peter; Vienhues, Jonas H.; Bedke, Tanja; Javidi, Ehsan; Rissiek, Björn; Jank, Larissa; Brockmann, Leonie; Sandrock, Inga; Degenhardt, Karoline; Jander, Alina; Roth, Vanessa; Schädlich, Ines S.; Prinz, Immo; Flavell, Richard A.; Kobayashi, Yasushi; Renné, Thomas; Gerloff, Christian; Huber, Samuel; Magnus, Tim; Gelderblom, Mathias
  • Erschienen: Springer Science and Business Media LLC, 2021
  • Erschienen in: Journal of Neuroinflammation
  • Sprache: Englisch
  • DOI: 10.1186/s12974-021-02316-7
  • ISSN: 1742-2094
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>Lymphocytes have dichotomous functions in ischemic stroke. Regulatory T cells are protective, while IL-17A from innate lymphocytes promotes the infarct growth. With recent advances of T cell-subtype specific transgenic mouse models it now has become possible to study the complex interplay of T cell subpopulations in ischemic stroke.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>In a murine model of experimental stroke we analyzed the effects of IL-10 on the functional outcome for up to 14 days post-ischemia and defined the source of IL-10 in ischemic brains based on immunohistochemistry, flow cytometry, and bone-marrow chimeric mice. We used neutralizing IL-17A antibodies, intrathecal IL-10 injections, and transgenic mouse models which harbor a deletion of the IL-10R on distinct T cell subpopulations to further explore the interplay between IL-10 and IL-17A pathways in the ischemic brain.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>We demonstrate that IL-10 deficient mice exhibit significantly increased infarct sizes on days 3 and 7 and enlarged brain atrophy and impaired neurological outcome on day 14 following tMCAO. In ischemic brains IL-10 producing immune cells included regulatory T cells, macrophages, and microglia. Neutralization of IL-17A following stroke reversed the worse outcome in IL-10 deficient mice and intracerebral treatment with recombinant IL-10 revealed that IL-10 controlled IL-17A positive lymphocytes in ischemic brains. Importantly, IL-10 acted differentially on αβ and γδ T cells. IL-17A producing CD4<jats:sup>+</jats:sup> αβ T cells were directly controlled via their IL-10-receptor (IL-10R), whereas IL-10 by itself had no direct effect on the IL-17A production in γδ T cells. The control of the IL-17A production in γδ T cells depended on an intact IL10R signaling in regulatory T cells (Tregs).</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Taken together, our data indicate a key function of IL-10 in restricting the detrimental IL-17A-signaling in stroke and further supports that IL-17A is a therapeutic opportunity for stroke treatment.</jats:p> </jats:sec>
  • Zugangsstatus: Freier Zugang