Title: | Myeloid differentiation factor 88 signaling in donor T cells accelerates graft-versus-host disease |
Authors: | Matsuoka, Satomi Browse this author |
Hashimoto, Daigo Browse this author →KAKEN DB |
Kadowaki, Masanori Browse this author |
Ohigashi, Hiroyuki Browse this author |
Hayase, Eiko Browse this author |
Yokoyama, Emi Browse this author |
Hasegawa, Yuta Browse this author |
Tateno, Takahiro Browse this author |
Chen, Xuanzhong Browse this author |
Aoyama, Kazutoshi Browse this author |
Oka, Hideyo Browse this author |
Onozawa, Masahiro Browse this author →KAKEN DB |
Takeda, Kiyoshi Browse this author →KAKEN DB |
Akashi, Koichi Browse this author →KAKEN DB |
Teshima, Takanori Browse this author →KAKEN DB |
Issue Date: | 1-Jan-2020 |
Publisher: | Ferrata Storti Foundation |
Journal Title: | Haematologica |
Volume: | 105 |
Issue: | 1 |
Start Page: | 226 |
End Page: | 234 |
Publisher DOI: | 10.3324/haematol.2018.203380 |
Abstract: | 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 NF kappa B 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 receptor-associated kinase 4 pathway is a novel therapeutic target against GvHD after allo-SCT. |
Rights: | https://creativecommons.org/licenses/by-nc/4.0/ |
Type: | article |
URI: | http://hdl.handle.net/2115/76613 |
Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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