| First Author | Matsuoka S | Year | 2020 |
| Journal | Haematologica | Volume | 105 |
| Issue | 1 | Pages | 226-234 |
| PubMed ID | 31048358 | Mgi Jnum | J:347399 |
| Mgi Id | MGI:6718071 | Doi | 10.3324/haematol.2018.203380 |
| Citation | Matsuoka S, et al. (2020) Myeloid differentiation factor 88 signaling in donor T cells accelerates graft-versus-host disease. Haematologica 105(1):226-234 |
| abstractText | 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 NFkappaB 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. |
