title: High-mobility group box 1 accelerates early acute allograft rejection via enhancing IL-17+ γδ T-cell response.
abstract: Th17 and γδ 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 γδ 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 γδ 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(+) γδ T-cell response and inhibited the gene transcription of IL-23 and IL-1β. Furthermore, in vitro HMGB1 indirectly promoted the development of IL-17(+) γδ T cells by stimulating dendritic cells to produce IL-23 and IL-1β, meanwhile depletion of γδ 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(+) γδ T-cell response by promoting the secretion of IL-23 and IL-1β, while IL-17(+) γδ T cells contribute to the early stage of acute allograft rejection.
authors.affiliation: Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Quansong
authors.initials: Q
authors.lastname: Xia
authors.forename: Lihua
authors.initials: L
authors.lastname: Duan
authors.forename: Lifeng
authors.initials: L
authors.lastname: Shi
authors.forename: Fang
authors.initials: F
authors.lastname: Zheng
authors.forename: Feili
authors.initials: F
authors.lastname: Gong
authors.forename: Min
authors.initials: M
authors.lastname: Fang
mesh_terms: D000208:Acute Disease; D064591:Allografts; D000818:Animals; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D006084:Graft Rejection / Q000209:etiology* / Q000276:immunology; D024243:HMGB1 Protein / Q000276:immunology* / Q000378:metabolism; D016027:Heart Transplantation / Q000009:adverse effects; D020381:Interleukin-17 / Q000096:biosynthesis; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000235:genetics; D053759:Interleukin-23 / Q000096:biosynthesis / Q000235:genetics; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000145:classification / Q000276:immunology; D058504:Th17 Cells / Q000145:classification / Q000276:immunology*
chemical_list: D024243:HMGB1 Protein; C582808:HMGB1 protein, mouse; D020381:Interleukin-17; D053583:Interleukin-1beta; D053759:Interleukin-23; D012333:RNA, Messenger; D016692:Receptors, Antigen, T-Cell, gamma-delta
keywords: IL-17+ γδ T cells; IL-23; acute allograft rejection; high-mobility group box 1