title: Deficiency of C5aR prolongs renal allograft survival.
abstract: Interaction between C5a, a product of complement activation, and its receptor (C5aR) upregulates antigen-specific T cell responses by modulating the activation of antigen-presenting cells and T cells. Whether this C5a-C5aR interaction contributes to the immune responses that promote renal allograft rejection is unknown. Here, we found that deficiency of C5aR in both graft and recipient reduced allospecific T cell responses and prolonged renal allograft survival. In addition, lack of C5aR impaired the function of donor and recipient antigen-presenting cells and inhibited the response of recipient T cells to allostimulation. Furthermore, deficiency of C5aR in both graft and recipient reduced early inflammation in the grafts, with less cellular infiltration around the vessels and fewer F4/80 positive cells in the peritubular interstitium. These data demonstrate that C5aR is critical for a full adaptive immune response and mediates renal allograft rejection. Engagement of C5aR on dendritic cells and T cells modulates their function, enhancing allospecific T cell responses that lead to allograft rejection. Targeting C5a signaling may have therapeutic potential for T cell-mediated graft rejection.
authors.affiliation: Department of Nephrology and Transplantation, MRC Centre for Transplantation, King's College London, School of Medicine at Guy's Hospital, London, UK.
authors.forename: Qijun
authors.initials: Q
authors.lastname: Li
authors.forename: Qi
authors.initials: Q
authors.lastname: Peng
authors.forename: Guolan
authors.initials: G
authors.lastname: Xing
authors.forename: Ke
authors.initials: K
authors.lastname: Li
authors.forename: Naiyin
authors.initials: N
authors.lastname: Wang
authors.forename: Conrad A
authors.initials: CA
authors.lastname: Farrar
authors.forename: Lucy
authors.initials: L
authors.lastname: Meader
authors.forename: Steven H
authors.initials: SH
authors.lastname: Sacks
authors.forename: Wuding
authors.initials: W
authors.lastname: Zhou
mesh_terms: D000818:Animals; D006085:Graft Survival / Q000276:immunology; D016030:Kidney Transplantation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D044087:Receptor, Anaphylatoxin C5a / Q000172:deficiency*; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors
chemical_list: D044087:Receptor, Anaphylatoxin C5a