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

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

in: J NEUROINFLAMM, Jahrgang 18, Nr. 1, 265, 13.11.2021.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Piepke, M, Clausen, BH, Ludewig, P, Vienhues, JH, Bedke, T, Javidi, E, Rissiek, B, Jank, L, Brockmann, L, Sandrock, I, Degenhardt, K, Jander, A, Roth, V, Schädlich, IS, Prinz, I, Flavell, RA, Kobayashi, Y, Renné, T, Gerloff, C, Huber, S, Magnus, T & Gelderblom, M 2021, 'Interleukin-10 improves stroke outcome by controlling the detrimental Interleukin-17A response', J NEUROINFLAMM, Jg. 18, Nr. 1, 265. https://doi.org/10.1186/s12974-021-02316-7

APA

Piepke, M., Clausen, B. H., Ludewig, P., Vienhues, J. H., Bedke, T., Javidi, E., Rissiek, B., Jank, L., Brockmann, L., Sandrock, I., Degenhardt, K., Jander, A., Roth, V., Schädlich, I. S., Prinz, I., Flavell, R. A., Kobayashi, Y., Renné, T., Gerloff, C., ... Gelderblom, M. (2021). Interleukin-10 improves stroke outcome by controlling the detrimental Interleukin-17A response. J NEUROINFLAMM, 18(1), [265]. https://doi.org/10.1186/s12974-021-02316-7

Vancouver

Piepke M, Clausen BH, Ludewig P, Vienhues JH, Bedke T, Javidi E et al. Interleukin-10 improves stroke outcome by controlling the detrimental Interleukin-17A response. J NEUROINFLAMM. 2021 Nov 13;18(1). 265. https://doi.org/10.1186/s12974-021-02316-7

Bibtex

@article{12c9f9061ad341ca9c23bfd65a959f5a,
title = "Interleukin-10 improves stroke outcome by controlling the detrimental Interleukin-17A response",
abstract = "BACKGROUND: 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.METHODS: 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.RESULTS: 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+ 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).CONCLUSIONS: 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.",
author = "Marius Piepke and Clausen, {Bettina H} and Peter Ludewig and Vienhues, {Jonas H} and Tanja Bedke and Ehsan Javidi and Bj{\"o}rn Rissiek and Larissa Jank and Leonie Brockmann and Inga Sandrock and Karoline Degenhardt and Alina Jander and Vanessa Roth and Sch{\"a}dlich, {Ines S} and Immo Prinz and Flavell, {Richard A} and Yasushi Kobayashi and Thomas Renn{\'e} and Christian Gerloff and Samuel Huber and Tim Magnus and Mathias Gelderblom",
note = "{\textcopyright} 2021. The Author(s).",
year = "2021",
month = nov,
day = "13",
doi = "10.1186/s12974-021-02316-7",
language = "English",
volume = "18",
journal = "J NEUROINFLAMM",
issn = "1742-2094",
publisher = "BioMed Central Ltd.",
number = "1",

}

RIS

TY - JOUR

T1 - Interleukin-10 improves stroke outcome by controlling the detrimental Interleukin-17A response

AU - Piepke, Marius

AU - Clausen, Bettina H

AU - Ludewig, Peter

AU - Vienhues, Jonas H

AU - Bedke, Tanja

AU - Javidi, Ehsan

AU - Rissiek, Björn

AU - Jank, Larissa

AU - Brockmann, Leonie

AU - Sandrock, Inga

AU - Degenhardt, Karoline

AU - Jander, Alina

AU - Roth, Vanessa

AU - Schädlich, Ines S

AU - Prinz, Immo

AU - Flavell, Richard A

AU - Kobayashi, Yasushi

AU - Renné, Thomas

AU - Gerloff, Christian

AU - Huber, Samuel

AU - Magnus, Tim

AU - Gelderblom, Mathias

N1 - © 2021. The Author(s).

PY - 2021/11/13

Y1 - 2021/11/13

N2 - BACKGROUND: 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.METHODS: 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.RESULTS: 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+ 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).CONCLUSIONS: 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.

AB - BACKGROUND: 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.METHODS: 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.RESULTS: 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+ 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).CONCLUSIONS: 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.

U2 - 10.1186/s12974-021-02316-7

DO - 10.1186/s12974-021-02316-7

M3 - SCORING: Journal article

C2 - 34772416

VL - 18

JO - J NEUROINFLAMM

JF - J NEUROINFLAMM

SN - 1742-2094

IS - 1

M1 - 265

ER -