High-mobility group box 1 accelerates early acute allograft rejection via enhancing IL-17+ γδ T-cell response

Th17 and gamma delta T cells are the dominant IL-17-producing cell. We previously reported that high-mobility group box 1 (HMGB1) is critical in inducing IL-17-producing alloreactive T cells during early stage of acute allograft rejection. However, the role of gamma delta T cells during this process and its implication in HMGB1-mediated allograft rejection are not fully understood. Here, we use a murine model of cardiac allograft transplantation to further study the role of HMGB1 and IL-17-producing gamma delta T cells in acute allograft rejection. It was found that the expression of HMGB1 was increased in allograft, while blockade of HMGB1 suppressed IL-17(+) gamma delta T-cell response and inhibited the gene transcription of IL-23 and IL-1 beta. Furthermore, in vitro HMGB1 indirectly promoted the development of IL-17(+) gamma delta T cells by stimulating dendritic cells to produce IL-23 and IL-1 beta, meanwhile depletion of gamma delta T cells in vivo prolonged allograft survival and reduced the level of IL-17 in serum. In conclusion, our findings inferred that increased HMGB1 expression could enhance IL-17(+) gamma delta T-cell response by promoting the secretion of IL-23 and IL-1 beta, while IL-17(+) gamma delta T cells contribute to the early stage of acute allograft rejection.