Boosting regulatory T cells limits neuroinflammation in permanent cortical stroke

• Verfasst von: Liesz, Arthur [VerfasserIn]
• Verfasst von: Zhou, Wei [VerfasserIn]
• Verfasst von: Na, Shin-Young [VerfasserIn]
• Verfasst von: Hämmerling, Günter J. [VerfasserIn]
• Verfasst von: Garbi, Natalio [VerfasserIn]
• Verfasst von: Karcher-Bausch, Simone [VerfasserIn]
• Verfasst von: Mracskó, Eva [VerfasserIn]
• Verfasst von: Backs, Johannes [VerfasserIn]
• Verfasst von: Rivest, Serge [VerfasserIn]
• Verfasst von: Veltkamp, Roland [VerfasserIn]
• Titel: Boosting regulatory T cells limits neuroinflammation in permanent cortical stroke
• Verf.angabe: Arthur Liesz, Wei Zhou, Shin-Young Na, Günter J. Hämmerling, Natalio Garbi, Simone Karcher, Eva Mracsko, Johannes Backs, Serge Rivest, and Roland Veltkamp
• E-Jahr: 2013
• Jahr: October 30, 2013
• Umfang: 13 S.
• Fussnoten: Gesehen am 03.03.2022
• Titel Quelle: Enthalten in: The journal of neuroscience
• Ort Quelle: Washington, DC : Soc., 1981
• Jahr Quelle: 2013
• Band/Heft Quelle: 33(2013), 44 vom: Okt., Seite 17350-17362
• ISSN Quelle: 1529-2401
• DOI: doi:10.1523/JNEUROSCI.4901-12.2013
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1794537201

Abstract

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.