Myeloid differentiation factor 88 signaling in donor T cells accelerates graft-versus-host disease

Satomi Matsuoka, Daigo Hashimoto, Masanori Kadowaki, Hiroyuki Ohigashi, Eiko Hayase, Emi Yokoyama, Yuta Hasegawa, Takahiro Tateno, Xuanzhong Chen, Kazutoshi Aoyama, Hideyo Oka, Masahiro Onozawa, Kiyoshi Takeda, Koichi Akashi, Takanori Teshima

研究成果: Contribution to journalArticle

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Myeloid differentiation factor 88 (MyD88) signaling has a crucial role in activation of both innate and adoptive immunity. MyD88 transduces signals via Toll-like receptor and interleukin-1 receptor superfamily to the NFkB pathway and inflammasome by forming a molecular complex with interleukin-1 receptor-associated kinase 4. The MyD88/interleukin-1 receptor-associated kinase 4 pathway plays an important role, not only in innate immunity, but also T-cell immunity; however, its role in donor T cells on the pathophysiology of graft-versus-host disease (GvHD) remains to be elucidated. We addressed this issue by using MyD88-deficient T cells in a mouse model of allogeneic hematopoietic stem cell transplantation (allo-SCT). While MyD88-deficient and wild-type T cells proliferated equivalently after transplantation, MyD88-deficient T cells demonstrated impaired survival and differentiation toward Th1, Tc1, and Th17, and induced less severe GvHD compared to wild-type T cells. Administration of interleukin-1 receptor-associated kinase 4 inhibitor PF-06650833 significantly ameliorated GvHD after allo-SCT. These results thus demonstrate that donor T-cell MyD88/ interleukin-1 receptor-associated kinase 4 pathway is a novel therapeutic target against GvHD after allo-SCT.

元の言語英語
ページ(範囲)226-234
ページ数9
ジャーナルHaematologica
105
発行部数1
DOI
出版物ステータス出版済み - 2020

All Science Journal Classification (ASJC) codes

  • Hematology

フィンガープリント Myeloid differentiation factor 88 signaling in donor T cells accelerates graft-versus-host disease' の研究トピックを掘り下げます。これらはともに一意のフィンガープリントを構成します。

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    Matsuoka, S., Hashimoto, D., Kadowaki, M., Ohigashi, H., Hayase, E., Yokoyama, E., Hasegawa, Y., Tateno, T., Chen, X., Aoyama, K., Oka, H., Onozawa, M., Takeda, K., Akashi, K., & Teshima, T. (2020). Myeloid differentiation factor 88 signaling in donor T cells accelerates graft-versus-host disease. Haematologica, 105(1), 226-234. https://doi.org/10.3324/haematol.2018.203380