α-Mannan induces Th17-mediated pulmonary graft-versus-host disease in mice.
α-Mannan induces Th17-mediated pulmonary graft-versus-host disease in mice.
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DOI：
10.1182/blood-2014-12-615781
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发表时间：
2015-05
期刊：
影响因子：
20.3
通讯作者：
H. Uryu;D. Hashimoto;Koji Kato;Eiko Hayase;S. Matsuoka;Reiki Ogasawara;Shuichiro Takahashi;Y. Maeda;H. Iwasaki;T. Miyamoto;S. Saijo;Y. Iwakura;G. Hill;K. Akashi;T. Teshima
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文献类型：
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作者：
H. Uryu;D. Hashimoto;Koji Kato;Eiko Hayase;S. Matsuoka;Reiki Ogasawara;Shuichiro Takahashi;Y. Maeda;H. Iwasaki;T. Miyamoto;S. Saijo;Y. Iwakura;G. Hill;K. Akashi;T. Teshima
异基因造血干细胞移植（HSCT）是治疗多种造血疾病的一种治疗方法。移植物抗宿主病（GVHD）和感染是HSCT的主要障碍，并且已表明它们之间存在密切关系。尽管细菌和病毒感染在 GVHD 病理生理学中的作用已得到很好的描述，但真菌感染对 GVHD 的影响仍有待阐明。在 GVHD 小鼠模型中，注射真菌细胞壁的主要成分 α-甘露聚糖 (Mn) 或热灭活的白色念珠菌会加剧 GVHD，特别是在肺部。 Mn 诱导供体 T 细胞向 Th17 极化，并且 GVHD 中肺部特异性趋化因子环境导致 Th17 细胞在肺部积聚。 Mn 对 GVHD 的有害影响取决于供体 IL-17A 的产生和宿主 C 型凝集素受体 Dectin-2。这些结果表明，肺部 GVHD 与同种异体 HSCT 后真菌感染之间存在先前未被认识的联系。
Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative therapy for various hematopoietic disorders. Graft-versus-host disease (GVHD) and infections are the major obstacles of HSCT, and their close relationship has been suggested. Although roles of bacterial and viral infections in the pathophysiology of GVHD are well described, impacts of fungal infection on GVHD remain to be elucidated. In mouse models of GVHD, injection of α-mannan (Mn), a major component of fungal cell wall, or heat-killed Candida albicans exacerbated GVHD, particularly in the lung. Mn-induced donor T-cell polarization toward Th17 and lung-specific chemokine environment in GVHD led to accumulation of Th17 cells in the lung. The detrimental effects of Mn on GVHD depended on donor IL-17A production and host C-type lectin receptor Dectin-2. These results suggest a previously unrecognized link between pulmonary GVHD and fungal infection after allogeneic HSCT.