Title:Adoptive Regulatory T-cell Therapy Attenuates Subarachnoid Hemor-rhage-induced Cerebral Inflammation by Suppressing TLR4/NF-B Signaling Pathway
Volume: 13
Issue: 2
Author(s): Yuan Wang, Leilei Mao, Lei Zhang, Liping Zhang, Mingfeng Yang, Zongyong Zhang, Dawei Li, Cundong Fan and Baoliang Sun
Affiliation:
Keywords:
Treg, Subarachnoid hemorrhage, matrix metallopeptidase 9 (MMP9), inflammation, TLR4, NF-κB.
Abstract: Inflammation is one major cause of poor outcomes of subarachnoid hemorrhage (SAH). The recent evidence
suggested that adoptive regulatory T-cell (Treg) therapy conferred potential neuroprotection by suppressing cerebral inflammation
against cerebral ischemia. Therefore, we proposed that Treg transfer might protect the brain against SAH by
decreasing cerebral inflammation. In this study, we injected the autologous blood into cisterna magna twice to make the
SAH model and administrated Tregs by vein to SAH rats. Intriguingly, adoptive transfer of Tregs significantly ameliorated
SAH-induced brain edema and increased cerebral blood flow. Moreover, Treg-afforded cerebral protection was accompanied
by suppressing SAH-induced cerebral inflammation. Concurrently, administration of Tregs attenuated the activation
of the toll-like receptor 4 and nuclear factor-kappa B (TLR4/NF-κB) signaling pathway, which should be involved
in the suppression of SAH-induced cerebral inflammation. Altogether, our study suggested that Treg adoptive
transfer could attenuate SAH-induced cerebral inflammation by suppressing the activation of the TLR4/NF-κB signaling
pathway, and thus provided new insights into the potent Treg cells-based therapy specifically targeting on post-SAH inflammatory
dysregulation.