Adoptively transferred donor IL-17-producing CD4+ T cells augment, but IL-17 alleviates, acute graft-versus-host disease
Adoptively transferred donor IL-17-producing CD4+ T cells augment, but IL-17 alleviates, acute graft-versus-host disease
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过继转移的供体产生 IL-17 的 CD4(+) T 细胞增强了急性移植物抗宿主病，但 IL-17 减轻了急性移植物抗宿主病
DOI：
10.1038/cmi.2016.37
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发表时间：
2018-03-01
影响因子：
24.1
通讯作者：
Liu, Haiyan
中科院分区：
文献类型：
--
作者：
Cai, Yifeng;Ma, Shoubao;Liu, Haiyan
IL-17和产生IL-17的CD4+T细胞在急性移植物抗宿主病（GVHD）中的作用在最近的小鼠和人类研究中一直存在争议。我们在完全主要组织相容性复合物错配清髓性骨髓移植的小鼠急性 GVHD 模型中进行了研究。我们发现，与IL-17(-/-) CD4(+) T 细胞相比，供体野生型CD4(+) T 细胞加剧了急性GVHD，而IL-17 则减轻了急性GVHD 的严重程度。转移的供体产生IL-17的CD4+T细胞对急性GVHD的增强与Th1反应的增加有关，而IL-17降低了GVHD靶器官中Th1细胞的百分比。此外，IL-17 减少了巨噬细胞向 GVHD 组织的浸润。体外研究表明，IL-17 可能通过抑制供体巨噬细胞产生 IL-12 来下调 Th1 反应。体内巨噬细胞的耗竭降低了 IL-17 的保护作用。我们的结果证明了过继转移的供体产生IL-17的CD4+T细胞和IL-17在同一急性GVHD模型中的不同作用。
The role of IL-17 and IL-17-producing CD4(+) T cells in acute graft-versus-host disease ( GVHD) has been controversial in recent mouse and human studies. We carried out studies in a murine acute GVHD model of fully major histocompatibility complex-mismatched myeloablative bone marrow transplantation. We showed that donor wild-type CD4(+) T cells exacerbated acute GVHD compared with IL-17(-/-) CD4(+) T cells, while IL-17 reduced the severity of acute GVHD. The augmentation of acute GVHD by transferred donor IL-17-producing CD4(+) T cells was associated with increased Th1 responses, while IL-17 decreased the percentages of Th1 cells in the GVHD target organs. Furthermore, IL-17 reduced the infiltration of macrophages into the GVHD tissues. In vitro study showed that IL-17 could downregulate Th1 responses, possibly through inhibiting IL-12 production by donor macrophages. Depletion of macrophages in vivo diminished the protective effect of IL-17. Our results demonstrated the differential roles of adoptively transferred donor IL-17-producing CD4(+) T cells and IL-17 in the same acute GVHD model.