Adoptive Regulatory T-cell Therapy Attenuates Subarachnoid Hemor-rhage-induced Cerebral Inflammation by Suppressing TLR4/NF-B Signaling Pathway

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-kappa B) 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-kappa B signaling pathway, and thus provided new insights into the potent Treg cells-based therapy specifically targeting on post-SAH inflammatory dysregulation.