The anthelmintic drug praziquantel promotes human Tr1 differentiation
The anthelmintic drug praziquantel promotes human Tr1 differentiation
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DOI：
10.1111/imcb.12229
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发表时间：
2019-05-01
影响因子：
4
通讯作者：
Astier, Anne L.
中科院分区：
文献类型：
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作者：
Eyoh, Enwono;McCallum, Patrick;Astier, Anne L.
吡喹酮（PZQ）是一种用于治疗吸虫和寄生虫的人类和兽药。免疫反应的变化已被证明在人类治疗血吸虫感染后的PZQ治疗。这些变化归因于免疫抑制蠕虫的去除和对垂死蠕虫暴露的寄生虫抗原的免疫反应。迄今为止，尚未有研究调查PZQ对宿主免疫细胞的潜在直接影响。在此，我们分析了PZQ对CD3/CD28共刺激或补体调节剂CD46共刺激诱导1型调节性T细胞（Tr1）的人CD4(+) T细胞的影响。我们的研究结果表明，PZQ能促进t细胞增殖，增加IL-17和IL-10的分泌，但对GM-CSF和IFN γ的分泌没有影响。此外，PZQ增加了Tr1细胞的标志CD49b和LAG-3的共表达，表明Tr1分化增加。事实上，pzq处理细胞的上清液能够降低旁观者t细胞的激活，并且当阻断IL-10时，这种作用部分降低。因此，我们的研究表明PZQ直接调节人类t细胞活化，促进Tr1分化，提示PZQ可能在与寄生虫无关的人类炎症性疾病中具有免疫调节功能。
Praziquantel (PZQ) is an anthelminthic human and veterinary drug used to treat trematode and cestode worms. Changes in immune responses have been demonstrated in humans following curative PZQ treatment of schistosome infections. These changes have been attributed to the removal of immunosupressive worms and immune responses to parasite antigens exposed from dying worms. To date, there has been no study investigating the potential direct effect of PZQ on the host immune cells. Herein, we analyzed the effect of PZQ on human CD4(+) T cells classically costimulated by CD3/CD28 or costimulated by the complement regulator CD46 to induce Type 1 regulatory T cells (Tr1). Our results show that PZQ enhanced T-cell proliferation, increased secretion of IL-17 and IL-10 but had no effect on secretion of GM-CSF or IFN gamma. Moreover, PZQ increased the coexpression of CD49b and LAG-3, a hallmark of Tr1 cells, suggesting increased Tr1 differentiation. Indeed, supernatants from PZQ-treated cells were able to decrease bystander T-cell activation, and this was partly reduced when blocking IL-10. Hence, our study demonstrates that PZQ directly modulates human T-cell activation and promotes Tr1 differentiation, suggesting that PZQ may have immunomodulatory functions in parasite-unrelated human inflammatory diseases.