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Boosting regulatory T cells limits neuroinflammation in permanent cortical stroke

Inflammatory mechanisms contribute substantially to secondary tissue injury after brain ischemia. Regulatory T cells (Tregs) are key endogenous modulators of postischemic neuroinflammation. We investigated the potential of histone deacetylase inhibition (HDACi) to enhance Treg potency for experiment...

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Hauptverfasser: Liesz, Arthur (VerfasserIn) , Zhou, Wei (VerfasserIn) , Na, Shin-Young (VerfasserIn) , Hämmerling, Günter J. (VerfasserIn) , Garbi, Natalio (VerfasserIn) , Karcher-Bausch, Simone (VerfasserIn) , Mracskó, Eva (VerfasserIn) , Backs, Johannes (VerfasserIn) , Rivest, Serge (VerfasserIn) , Veltkamp, Roland (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: October 30, 2013
In: The journal of neuroscience
Year: 2013, Jahrgang: 33, Heft: 44, Pages: 17350-17362
ISSN:1529-2401
DOI:10.1523/JNEUROSCI.4901-12.2013
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1523/JNEUROSCI.4901-12.2013
Verlag, lizenzpflichtig, Volltext: https://www.jneurosci.org/content/33/44/17350
Volltext
Verfasserangaben:Arthur Liesz, Wei Zhou, Shin-Young Na, Günter J. Hämmerling, Natalio Garbi, Simone Karcher, Eva Mracsko, Johannes Backs, Serge Rivest, and Roland Veltkamp
Beschreibung
Zusammenfassung:Inflammatory mechanisms contribute substantially to secondary tissue injury after brain ischemia. Regulatory T cells (Tregs) are key endogenous modulators of postischemic neuroinflammation. We investigated the potential of histone deacetylase inhibition (HDACi) to enhance Treg potency for experimental stroke in mice. HDACi using trichostatin A increased the number of Tregs and boosted their immunosuppressive capacity and interleukin (IL)-10 expression. In vivo treatment reduced infarct volumes and behavioral deficits after cortical brain ischemia, attenuated cerebral proinflammatory cytokine expression, and increased numbers of brain-invading Tregs. A similar effect was obtained using tubastatin, a specific inhibitor of HDAC6 and a key HDAC in Foxp3 regulation. The neuroprotective effect of HDACi depended on the presence of Foxp3+ Tregs, and in vivo and in vitro studies showed that the anti-inflammatory cytokine IL-10 was their main mediator. In summary, modulation of Treg function by HDACi is a novel and potent target to intervene at the center of neuroinflammation. Furthermore, this novel concept of modulating endogenous immune mechanisms might be translated to a broad spectrum of diseases, including primary neuroinflammatory and neurodegenerative disorders.
Beschreibung:Gesehen am 03.03.2022
Beschreibung:Online Resource
ISSN:1529-2401
DOI:10.1523/JNEUROSCI.4901-12.2013

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