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

Research output: Contribution to journalArticle

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 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.

Original languageEnglish
Pages (from-to)226-234
Number of pages9
JournalHaematologica
Volume105
Issue number1
DOIs
Publication statusPublished - Jan 1 2020

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Myeloid Differentiation Factor 88
Graft vs Host Disease
Interleukin-1 Receptor-Associated Kinases
T-Lymphocytes
Hematopoietic Stem Cell Transplantation
Innate Immunity
Toll-Like Receptor 1
Inflammasomes
Interleukin-1 Receptors
Adaptive Immunity
Cell Differentiation
Immunity
Transplantation

All Science Journal Classification (ASJC) codes

  • Hematology

Cite this

Matsuoka, S., Hashimoto, D., Kadowaki, M., Ohigashi, H., Hayase, E., Yokoyama, E., ... 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

Myeloid differentiation factor 88 signaling in donor T cells accelerates graft-versus-host disease. / Matsuoka, Satomi; Hashimoto, Daigo; Kadowaki, Masanori; Ohigashi, Hiroyuki; Hayase, Eiko; Yokoyama, Emi; Hasegawa, Yuta; Tateno, Takahiro; Chen, Xuanzhong; Aoyama, Kazutoshi; Oka, Hideyo; Onozawa, Masahiro; Takeda, Kiyoshi; Akashi, Koichi; Teshima, Takanori.

In: Haematologica, Vol. 105, No. 1, 01.01.2020, p. 226-234.

Research output: Contribution to journalArticle

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, vol. 105, no. 1, pp. 226-234. https://doi.org/10.3324/haematol.2018.203380
Matsuoka S, Hashimoto D, Kadowaki M, Ohigashi H, Hayase E, Yokoyama E et al. Myeloid differentiation factor 88 signaling in donor T cells accelerates graft-versus-host disease. Haematologica. 2020 Jan 1;105(1):226-234. https://doi.org/10.3324/haematol.2018.203380
Matsuoka, Satomi ; Hashimoto, Daigo ; Kadowaki, Masanori ; Ohigashi, Hiroyuki ; Hayase, Eiko ; Yokoyama, Emi ; Hasegawa, Yuta ; Tateno, Takahiro ; Chen, Xuanzhong ; Aoyama, Kazutoshi ; Oka, Hideyo ; Onozawa, Masahiro ; Takeda, Kiyoshi ; Akashi, Koichi ; Teshima, Takanori. / Myeloid differentiation factor 88 signaling in donor T cells accelerates graft-versus-host disease. In: Haematologica. 2020 ; Vol. 105, No. 1. pp. 226-234.
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