TY - JOUR AU - Satomi Matsuoka, AU - Daigo Hashimoto, AU - Masanori Kadowaki, AU - Hiroyuki Ohigashi, AU - Eiko Hayase, AU - Emi Yokoyama, AU - Yuta Hasegawa, AU - Takahiro Tateno, AU - Xuanzhong Chen, AU - Kazutoshi Aoyama, AU - Hideyo Oka, AU - Masahiro Onozawa, AU - Kiyoshi Takeda, AU - Koichi Akashi, AU - Takanori Teshima, PY - 2020/01/01 Y2 - 2024/03/29 TI - Myeloid differentiation factor 88 signaling in donor T cells accelerates graft-versus-host disease JF - Haematologica JA - haematol VL - 105 IS - 1 SE - Articles DO - 10.3324/haematol.2018.203380 UR - https://haematologica.org/article/view/9492 SP - 226-234 AB - 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 NFκB 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. ER -