Faculty Opinions recommendation of Commensal microbiota affects ischemic stroke outcome by regulating intestinal γδ T cells.

2016 ◽  
Author(s):  
Martin Schwab
Keyword(s):  
T Cells ◽  
Ischemic Stroke ◽  
Γδ T Cells ◽  
Stroke Outcome ◽  
Commensal Microbiota

scholarly journals Commensal microbiota affects ischemic stroke outcome by regulating intestinal γδ T cells

2016 ◽  
Vol 22 (5) ◽  
pp. 516-523 ◽  
Author(s):  
Corinne Benakis ◽  
David Brea ◽  
Silvia Caballero ◽  
Giuseppe Faraco ◽  
Jamie Moore ◽  
...  
Keyword(s):  
T Cells ◽  
Ischemic Stroke ◽  
Γδ T Cells ◽  
Stroke Outcome ◽  
Commensal Microbiota

scholarly journals Inhibition of Perforin-Mediated Neurotoxicity Attenuates Neurological Deficits After Ischemic Stroke

2021 ◽  
Vol 15 ◽  
Author(s):  
Yuhualei Pan ◽  
Dan Tian ◽  
Huan Wang ◽  
Yushang Zhao ◽  
Chengjie Zhang ◽  
...  
Keyword(s):  
T Cells ◽  
Ischemic Stroke ◽  
Immune Cells ◽  
Infarct Volume ◽  
Γδ T Cells ◽  
Neurological Deficits ◽  
Wild Type ◽  
Critical Function ◽  
Ischemic Brain ◽  
Potential Strategy

Perforin-mediated cytotoxicity plays a crucial role in microbial defense, tumor surveillance, and primary autoimmune disorders. However, the contribution of the cytolytic protein perforin to ischemia-induced secondary tissue damage in the brain has not been fully investigated. Here, we examined the kinetics and subpopulations of perforin-positive cells and then evaluated the direct effects of perforin-mediated cytotoxicity on outcomes after ischemic stroke. Using flow cytometry, we showed that perforin+CD45+ immune cells could be detected at 12 h and that the percentage of these cells increased largely until on day 3 and then significantly declined on day 7. Surprisingly, the percentage of Perforin+CD45+ cells also unexpectedly increased from day 7 to day 14 after ischemic stroke in Perforin1-EGFP transgenic mice. Our results suggested that Perforin+CD45+ cells play vital roles in the ischemic brain at early and late stages and further suggested that Perforin+CD45+ cells are a heterogeneous population. Surprisingly, in addition to CD8+ T cells, NK cells, and NKT cells, central nervous system (CNS)-resident immune microglia, which are first triggered and activated within minutes after ischemic stroke in mice, also secreted perforin during ischemic brain injury. In our study, the percentage of perforin+ microglia increased from 12 h after ischemic stroke, increased largely until on day 3 after ischemic stroke, and then moderately declined from days 3 to 7. Intriguingly, the percentage of perforin+ microglia also dramatically increased from days 7 to 14 after ischemic stroke. Furthermore, compared with wild-type littermates, Perforin 1–/– mice exhibited significant increases in the cerebral infarct volume, neurological deficits, and neurogenesis and inhibition of neurotoxic astrogliosis. Interestingly, the number of CD45+CD3+ T cells was significantly decreased in Perforin 1–/– mice compared with their wild-type littermates, especially the number of γδ T cells. In addition, Perforin 1–/– mice had lower levels of IL-17 than their wild-type littermates. Our results identified a critical function of perforin-mediated neurotoxicity in the ischemic brain, suggesting that targeting perforin-mediated neurotoxicity in brain-resident microglia and invading perforin+CD45+ immune cells may be a potential strategy for the treatment of ischemic stroke.

Abstract A63: Commensal microbiota promote lung tumorigenesis via γδ T cells

2020 ◽  
Author(s):  
Chengcheng Jin ◽  
Chen Zhao ◽  
Georgia Lagoudas ◽  
Arjun Bhutkar ◽  
Bo Hu ◽  
...  
Keyword(s):  
T Cells ◽  
Γδ T Cells ◽  
Lung Tumorigenesis ◽  
Commensal Microbiota

scholarly journals Commensal Microbiota Promote Lung Cancer Development via γδ T Cells

Cell ◽  
2019 ◽  
Vol 176 (5) ◽  
pp. 998-1013.e16 ◽  
Author(s):  
Chengcheng Jin ◽  
Georgia K. Lagoudas ◽  
Chen Zhao ◽  
Susan Bullman ◽  
Arjun Bhutkar ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
Γδ T Cells ◽  
Cancer Development ◽  
Commensal Microbiota

scholarly journals CD109 Restrains Activation of Cutaneous IL-17-Producing γδ T Cells by Commensal Microbiota

Cell Reports ◽  
2019 ◽  
Vol 29 (2) ◽  
pp. 391-405.e5 ◽  
Author(s):  
Hualin Zhang ◽  
Giustino Carnevale ◽  
Barbara Polese ◽  
Melissa Simard ◽  
Bavanitha Thurairajah ◽  
...  
Keyword(s):  
T Cells ◽  
Γδ T Cells ◽  
Commensal Microbiota

scholarly journals Interleukin-10 Improves Stroke Outcome by Controlling the Detrimental Interleukin-17A Response

2021 ◽  
Author(s):  
Marius Piepke ◽  
Bettina H. Clausen ◽  
Peter Ludewig ◽  
Jonas H. Vienhues ◽  
Tanja Bedke ◽  
...  
Keyword(s):  
T Cells ◽  
Ischemic Stroke ◽  
T Cell ◽  
Regulatory T Cells ◽  
Mouse Models ◽  
Γδ T Cells ◽  
Transgenic Mouse Models ◽  
Cell Subpopulations ◽  
T Cell Subpopulations ◽  
Deficient Mice

Abstract Background: Lymphocytes have dichotomous functions in ischemic stroke. Regulatory T cells are protective, while IL-17A from innate lymphocytes promotes the infarcts 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 three and seven and enlarged brain atrophy and impaired neurological outcome on day fourteen 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.

scholarly journals Neutralization of the IL-17 axis diminishes neutrophil invasion and protects from ischemic stroke

Blood ◽  
2012 ◽  
Vol 120 (18) ◽  
pp. 3793-3802 ◽  
Author(s):  
Mathias Gelderblom ◽  
Anna Weymar ◽  
Christian Bernreuther ◽  
Joachim Velden ◽  
Priyadharshini Arunachalam ◽  
...  
Keyword(s):  
T Cells ◽  
Ischemic Stroke ◽  
Murine Model ◽  
Ischemia Reperfusion Injury ◽  
Therapeutic Option ◽  
Ischemia Reperfusion ◽  
Γδ T Cells ◽  
Tnf Α ◽  
Selective Targeting ◽  
Enhanced Secretion

Abstract The devastating effect of ischemic stroke is attenuated in mice lacking conventional and unconventional T cells, suggesting that inflammation enhances tissue damage in cerebral ischemia. We explored the functional role of αβ and γδ T cells in a murine model of stroke and distinguished 2 different T cell–dependent proinflammatory pathways in ischemia-reperfusion injury. IFN-γ produced by CD4+ T cells induced TNF-α production in macrophages, whereas IL-17A secreted by γδ T cells led to neutrophil recruitment. The synergistic effect of TNF-α and IL-17A on astrocytes resulted in enhanced secretion of CXCL-1, a neutrophil chemoattractant. Application of an IL-17A–blocking antibody within 3 hours after stroke induction decreased infarct size and improved neurologic outcome in the murine model. In autoptic brain tissue of patients who had a stroke, we detected IL-17A–positive lymphocytes, suggesting that this aspect of the inflammatory cascade is also relevant in the human brain. We propose that selective targeting of IL-17A signaling might provide a new therapeutic option for the treatment of stroke.

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

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Marius Piepke ◽  
Bettina H. Clausen ◽  
Peter Ludewig ◽  
Jonas H. Vienhues ◽  
Tanja Bedke ◽  
...  
Keyword(s):  
T Cells ◽  
Ischemic Stroke ◽  
T Cell ◽  
Regulatory T Cells ◽  
Mouse Models ◽  
Γδ T Cells ◽  
Transgenic Mouse Models ◽  
Cell Subpopulations ◽  
T Cell Subpopulations ◽  
Deficient Mice

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.

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