演題詳細

一般口演 / Oral Session

一般口演 22 (Oral Session 22) :造血幹細胞移植:基礎

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日程
2013年10月11日(金)
時間
15:25 - 16:25
会場
第5会場 / Room No.5 (さっぽろ芸文館 3F 清流)
座長・司会
村田 誠 (Makoto Murata):1
1:名古屋大学医学部附属病院 血液内科
 
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Fungal cell wall component induces Th17 response and accelerates acute GVHD in lung

演題番号 : OS-1-112

瓜生 英尚 (Hidetaka Uryu):1,2、下地 園子 (Sonoko Shimoji):1、江里口 芳裕 (Yoshihiro Eriguchi):1、高嶋 秀一郎 (Shuichiro Takashima):1、加藤 光次 (Koji Kato):1、赤司 浩一 (Koichi Akashi):1、豊嶋 崇徳 (Takanori Teshima):2

1:Department of Medicine and Biosystemic Science, Kyushu University, Japan、2:Department of Hematology, Hokkaido University, Japan

 

Fungal infection is a serious complication after allogeneic hematopoietic stem cell transplantation, but its impacts on GVHD are not well documented. We report that α-mannan, one of the main components of fungal cell wall, induces Th17 responses, leading to severe acute GVHD mainly in lung. Lethally irradiated B6D2F1 (H-2b/d) mice were injected with 4×106 BM and 4×106 T cells from MHC-mismatched B6(H-2b) donors on day0. Mice were intraperitoneally injected with α-mannan or diluent on day1. Morbidity and mortality of GVHD were significantly higher in α-mannan-treated allogeneic mice in a dose dependent manner. Histopathologic examination showed significant exacerbation of GVHD pathology, particularly in the lung of mannan-treated animals. Addition of mannan induced Th17 differentiation of T cells in vitro. Expression of RORc and IL-17 was increased in T cell isolated from the lung of mannan-treated allogeneic mice. We then evaluated the roles of Th17 in aGVHD of mannan-treated allogeneic models using IL-17-deficient mice as donors. Exacerbation of GVHD by administration of mannan was ameliorated in recipients of IL-17-/- T cells when assessed by GVHD clinical scores (3.5±0.4vs5.5±0.3 at day14, p<0.05),survival(62.5%vs12.5% at day30, p<0.05),and pulmonary GVHD pathology scores(1.0±0.5vs7.0±1.0 at day21, p<0.05) compared with recipients of wild-type.These results suggest that fungal infection is a risk for GVHD exacerbation primarily in the lung at least partly Th17-dependent mechanisms and that fungal infection prevention is important for the prevention of pulmonary GVHD.

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