Anti-prion activity of cellulose ether is impaired in mice lacking pre T-cell antigen receptor α, T-cell receptor δ, or lytic granule function
Anti-prion activity of cellulose ether is impaired in mice lacking pre T-cell antigen receptor α, T-cell receptor δ, or lytic granule function
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在缺乏前 T 细胞抗原受体 α、T 细胞受体 δ 或裂解颗粒功能的小鼠中，纤维素醚的抗朊病毒活性受损
DOI：
10.1016/j.intimp.2022.108672
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发表时间：
2022
影响因子：
5.6
通讯作者：
Doh-ura Katsumi
中科院分区：
文献类型：
--
作者：
Teruya Kenta;Oguma Ayumi;Takahashi Satoko;Watanabe-Matsui Miki;Tsuji-Kawahara Sachiyo;Miyazawa Masaaki;Doh-ura Katsumi
纤维素醚（CE）的抗朊病毒活性已在啮齿类动物中报道，但作用机制尚不清楚。由于Tga20小鼠中早期T细胞发育的缺陷已被报道，CE给药仅显示出轻微的影响，因此我们研究了CE作用中免疫功能的参与。我们证实了朊病毒蛋白转基因插入Tga 20小鼠的前T细胞抗原受体α基因，其在胸腺和其他组织中的表达受损。然后在用免疫抑制剂或新生胸腺切除术处理的高CE应答小鼠中检查免疫抑制对CE效应的影响。由于新生儿胸腺切除术显著降低了CE效应，我们比较了具有相似遗传背景的小鼠中各种T细胞缺陷的影响。在αβ T细胞谱系缺陷的小鼠中，CE效应增加或不变，而在T细胞受体δ缺陷的小鼠中，CE效应被消除。此外，当检查其他免疫缺陷时，CE效应在具有溶酶体运输功能障碍的小鼠中降低，但在B细胞分化或Toll样受体4信号传导缺陷的小鼠中不变。这些发现共同表明CE的作用机制可能涉及γδ T细胞和溶解颗粒功能，以及免疫因子如自然杀伤T细胞，这些细胞在前T细胞抗原受体α缺陷小鼠和胸腺切除小鼠中缺乏。
The anti-prion activity of cellulose ether (CE) has been reported in rodents, but the mechanism of action is not well understood. As defects in early T-cell development have been reported in Tga20 mice which show only a slight effect of CE administration, we investigated the involvement of immune functions in the CE action. We confirmed an insertion of the prion protein transgene into the pre T-cell antigen receptor α gene of Tga20 mice, and its impaired expression in the thymus and other tissues. The influence of immune suppression on the CE effect was then examined in high CE-responder mice treated with immunosuppressive agents or neonatal thymectomy. As neonatal thymectomy significantly reduced the CE effect, we compared the influence of various T-cell defects in mice with similar genetic backgrounds. The CE effect was increased or unchanged in mice with defects in the αβ T-cell lineage, whereas it was abolished in T-cell receptor δ deficient mice. Further, when other immune defects were examined, the CE effect was reduced in mice with lysosomal trafficking dysfunction, but was unchanged in mice deficient in B-cell differentiation or toll-like receptor 4 signaling. These findings collectively suggest that the mechanism of CE action may involve γδ T cells and lytic granule function, as well as immune factors like natural killer T cells which are lacking in pre T-cell antigen receptor α deficient mice and neonatally thymectomized mice.