α-Mannan induces Th17-mediated pulmonary graft-versus-host disease in mice

Hidetaka Uryu, Daigo Hashimoto, Koji Kato, Eiko Hayase, Satomi Matsuoka, Reiki Ogasawara, Shuichiro Takahashi, Yoshinobu Maeda, Hiromi Iwasaki, Toshihiro Miyamoto, Shinobu Saijo, Yoichiro Iwakura, Geoffrey R. Hill, Koichi Akashi, Takanori Teshima

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Abstract

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.

Original languageEnglish
Pages (from-to)3014-3023
Number of pages10
JournalBlood
Volume125
Issue number19
DOIs
Publication statusPublished - May 7 2015

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ASJC Scopus subject areas

  • Medicine(all)

Cite this

Uryu, H., Hashimoto, D., Kato, K., Hayase, E., Matsuoka, S., Ogasawara, R., Takahashi, S., Maeda, Y., Iwasaki, H., Miyamoto, T., Saijo, S., Iwakura, Y., Hill, G. R., Akashi, K., & Teshima, T. (2015). α-Mannan induces Th17-mediated pulmonary graft-versus-host disease in mice. Blood, 125(19), 3014-3023. https://doi.org/10.1182/blood-2014-12-615781