10月17日，Nature旗下的免疫学权威期刊Cellular & Molecular Immunology（影响因子: 5.193）以研究论文形式在线发表了我院吴德沛教授、刘海燕教授研究团队关于急性移植物抗宿主病（aGVHD）的最新研究成果“Adoptively transferred donor IL-17-producing CD4+ T cells augment, but IL-17 alleviates, acute graft-versus-host disease”。Th17细胞及其特征性细胞因子IL-17在aGVHD发病中的作用仍然不清楚，理清IL-17和Th17细胞的不同作用对于aGVHD的临床诊断和防治具有重要意义。
在吴德沛教授和刘海燕教授的指导下，蔡奕峰博士和马守宝博士利用IL-17A敲基因小鼠，在同一个aGVHD小鼠模型中深入研究了IL-17和Th17细胞在aGVHD发生发展中的不同作用及其免疫学机制。创新性的发现Th17细胞促进aGVHD，而IL-17细胞因子保护aGVHD的不同作用。机制研究表明Th17细胞在体内的表型不稳定，容易转变为促进aGVHD发病的Th1细胞；而IL-17细胞因子能够通过减少aGVHD靶器官中的巨噬细胞，抑制其分泌IL-12等炎症细胞因子，进而抑制靶器官中的Th1细胞，减轻aGVHD。
Cellular & Molecular Immunology在同期杂志上专门刊发了美国南卡罗来纳医科大学免疫系Xuezhong Yu教授的题为“IL-17A ≠ Th17 in GVHD”的评论文章，指出“This study clarifies the role of Th17 cells and IL-17A inGvHD and identifies a valid concern about targeting Th17 cells via IL-17A blockade for GvHD prevention”。因此，尽管临床上也发现IL-17及Th17细胞与aGVHD的发病具有相关性，但是靶向阻断IL-17可能不是防治aGVHD的有效手段。
该项研究得到了国家自然科学基金、江苏省自然科学基金以及江苏省高校优势学科等多项经费支持。
原文链接：http://www.nature.com/cmi/journal/vaop/ncurrent/full/cmi201637a.html
同期评论：http://www.nature.com/cmi/journal/vaop/ncurrent/full/cmi201654a.html
原文摘要：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.
