Brain regulatory T cells suppress astrogliosis and potentiate neurological recovery
Brain regulatory T cells suppress astrogliosis and potentiate neurological recovery
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DOI：
10.1038/s41586-018-0824-5
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发表时间：
2019-01-10
期刊：
影响因子：
64.8
通讯作者：
Yoshimura, Akihiko
中科院分区：
文献类型：
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作者：
Ito, Minako;Komai, Kyoko;Yoshimura, Akihiko
除了维持免疫耐受外，FOXP3（+）调节性T （T-reg）细胞在组织稳态和重塑中发挥特殊功能（1,2）。然而，由于正常情况下大脑中Treg细胞的数量很少，因此人们对大脑Treg细胞的特性和功能还不太了解。在这里，我们表明，在缺血性脑卒中后，小鼠大脑中有大量的T-reg细胞积累，这增强了缺血性脑损伤慢性期的神经恢复。尽管脑T-reg细胞与内脏脂肪组织和肌肉等其他组织中的Treg细胞相似（3-5），但它们明显不同，表达与神经系统相关的独特基因，包括编码5-羟色胺受体5-HT7的ht7。脑T- regg细胞的扩增依赖于白细胞介素(IL)-2、IL-33、血清素和T细胞受体识别，并由趋化因子CCL1和CCL20驱动其向脑内的浸润。脑t - regg细胞通过产生双调节蛋白（一种低亲和力表皮生长因子受体（EGFR）配体）抑制神经毒性星形胶质细胞形成。脑卒中是神经功能障碍的主要原因，目前除了慢性期的康复治疗外，几乎没有有效的康复方法。我们的研究结果表明，T-reg细胞及其产物可能为神经元保护提供治疗机会，以防止中风和神经炎症性疾病。
In addition to maintaining immune tolerance, FOXP3(+) regulatory T (T-reg) cells perform specialized functions in tissue homeostasis and remodelling(1,2). However, the characteristics and functions of brain Treg cells are not well understood because there is a low number of Treg cells in the brain under normal conditions. Here we show that there is massive accumulation of T-reg cells in the mouse brain after ischaemic stroke, and this potentiates neurological recovery during the chronic phase of ischaemic brain injury. Although brain T-reg cells are similar to Treg cells in other tissues such as visceral adipose tissue and muscle(3-5), they are apparently distinct and express unique genes related to the nervous system including Htr7, which encodes the serotonin receptor 5-HT7. The amplification of brain T-reg cells is dependent on interleukin (IL)-2, IL-33, serotonin and T cell receptor recognition, and infiltration into the brain is driven by the chemokines CCL1 and CCL20. Brain T-reg cells suppress neurotoxic astrogliosis by producing amphiregulin, a low-affinity epidermal growth factor receptor (EGFR) ligand. Stroke is a leading cause of neurological disability, and there are currently few effective recovery methods other than rehabilitation during the chronic phase. Our findings suggest that T-reg cells and their products may provide therapeutic opportunities for neuronal protection against stroke and neuroinflammatory diseases.