TY - JOUR
T1 - α-Mannan induces Th17-mediated pulmonary graft-versus-host disease in mice
AU - Uryu, Hidetaka
AU - Hashimoto, Daigo
AU - Kato, Koji
AU - Hayase, Eiko
AU - Matsuoka, Satomi
AU - Ogasawara, Reiki
AU - Takahashi, Shuichiro
AU - Maeda, Yoshinobu
AU - Iwasaki, Hiromi
AU - Miyamoto, Toshihiro
AU - Saijo, Shinobu
AU - Iwakura, Yoichiro
AU - Hill, Geoffrey R.
AU - Akashi, Koichi
AU - Teshima, Takanori
N1 - Publisher Copyright:
© 2015 by The American Society of Hematology.
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
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U2 - 10.1182/blood-2014-12-615781
DO - 10.1182/blood-2014-12-615781
M3 - Article
C2 - 25740827
AN - SCOPUS:84929199400
SN - 0006-4971
VL - 125
SP - 3014
EP - 3023
JO - Blood
JF - Blood
IS - 19
ER -