Myeloid differentiation factor 88 signaling in donor T cells accelerates graft-versus-host disease
| Autor: | Emi Yokoyama, Hiroyuki Ohigashi, Yuta Hasegawa, Xuanzhong Chen, Kazutoshi Aoyama, Satomi Matsuoka, Hideyo Oka, Eiko Hayase, Masanori Kadowaki, Masahiro Onozawa, Daigo Hashimoto, Koichi Akashi, Takahiro Tateno, Takanori Teshima, Kiyoshi Takeda |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Innate immune system
medicine.medical_treatment Inflammasome Hematology Hematopoietic stem cell transplantation Biology medicine.disease Transplantation surgical procedures operative Graft-versus-host disease Adoptive immunity Immunity medicine Cancer research Myeloid Differentiation Factor 88 medicine.drug |
| Zdroj: | Haematologica. 105(1):226-234 |
| ISSN: | 0390-6078 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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