Madeleine Ingelsten1, Karin Gustafsson, Michael Olausson, Börje Haraldsson, Alex Karlsson-Parra, Jenny Nyström. 1. 1 Department of Infectious Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden. 2 Department of Immunology, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden. 3 Department of Surgery, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden. 4 Department of Clinical and Molecular Medicine (Nephrology), Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden. 5 Department of Immunology, Genetics, and Pathology, Uppsala University, Uppsala, Sweden. 6 Department of Physiology, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden. 7 Address correspondence to: Jenny Nyström, Ph.D., Gothenburg University, Institute of Neuroscience and Physiology, Renal Physiology, P. O. Box 432, 40530 Gothenburg, Sweden.
Abstract
BACKGROUND: After transplantation, donor dendritic cells (DCs) in the grafted organ are activated by an ischemia/reperfusion-induced inflammatory process that induces their migration to the recipient's secondary lymphoid tissues. The subsequent interaction between migrated and mature donor DCs, recipient T cells, and natural killer (NK) cells is proposed to be crucial in directing host immune reactions toward allograft rejection. A liver transplant is less prone to induce rejection compared with most other solid organ transplants, and simultaneous transplantation of liver and kidney is known to improve the clinical outcome of kidney transplantation. METHODS AND RESULTS: Here we show that liver as well as combined auxiliary liver-kidney transplantation in patients induces a rapid increase in plasma interleukin-10 (IL-10) to levels that are significantly higher than those seen after standard kidney transplantation. Addition of IL-10 during in vitro maturation of human monocyte-derived DCs with ischemia/reperfusion-associated factors was found to affect phenotypic DC maturation significantly. Addition of IL-10 inhibited DC production of the NK cell- and T cell-recruiting chemokines CXCL9, CXCL10 and CXCL11. CONCLUSION: Our findings indicate that liver transplantation induces a substantial systemic release of IL-10, which may inhibit T cell- and NK cell-mediated rejection processes toward the transplanted liver and concurrently transplanted kidney.
BACKGROUND: After transplantation, donor dendritic cells (DCs) in the grafted organ are activated by an ischemia/reperfusion-induced inflammatory process that induces their migration to the recipient's secondary lymphoid tissues. The subsequent interaction between migrated and mature donor DCs, recipient T cells, and natural killer (NK) cells is proposed to be crucial in directing host immune reactions toward allograft rejection. A liver transplant is less prone to induce rejection compared with most other solid organ transplants, and simultaneous transplantation of liver and kidney is known to improve the clinical outcome of kidney transplantation. METHODS AND RESULTS: Here we show that liver as well as combined auxiliary liver-kidney transplantation in patients induces a rapid increase in plasma interleukin-10 (IL-10) to levels that are significantly higher than those seen after standard kidney transplantation. Addition of IL-10 during in vitro maturation of human monocyte-derived DCs with ischemia/reperfusion-associated factors was found to affect phenotypic DC maturation significantly. Addition of IL-10 inhibited DC production of the NK cell- and T cell-recruiting chemokines CXCL9, CXCL10 and CXCL11. CONCLUSION: Our findings indicate that liver transplantation induces a substantial systemic release of IL-10, which may inhibit T cell- and NK cell-mediated rejection processes toward the transplanted liver and concurrently transplanted kidney.
Authors: R J Arasaratnam; I Tzannou; T Gray; P I Aguayo-Hiraldo; M Kuvalekar; S Naik; A Gaikwad; H Liu; T Miloh; J F Vera; R W Himes; F M Munoz; A M Leen Journal: Am J Transplant Date: 2018-07-10 Impact factor: 8.086