A Novel Role of Innate Immune Responses (Toll-Like Receptor-4) in Triggering Graft-Versus-Host Disease

摘要

In this issue of Transplantation, Imado et al. (1) report a role for recipient toll-like receptor (TLR)-4 in triggering acute graft-versus-host disease (GVHD) in their article entitled "The protective role of host TLR-4 in acute GVHD." C3H/ Hej (TLR-4 mutant) mice receiving T-cell-depleted (TCD)-bone marrow cell (BMC) transplants from C57BL/6 donors developed more severe GVHD than C3H/HeN (TLR-4 intact) mice receiving similar treatment. In TLR-4 mutant mice, the severity of GVHD was associated with an increase in tumor necrosis factor (TNF)-alpha messenger RNA expression in the intestine and liver and an increase in serum lipopolysaccharide (LPS) levels. The majority of TNF-alpha-positive cells in the intestine were donor-derived macrophages. TLR-4 mutant GVHD mice exhibited decreased production of tissue protective factors such as COX-2, PGE2, and HGF, suggesting that host TLR-4 may play a protective role in acute GVHD.