Blockade or deficiency of PD-L1 expression in intestinal allograft accelerates graft tissue injury in mice.
Autor: | Matsushima H; Department of General Surgery, Digestive Disease & Surgery Institute, Cleveland Clinic, Cleveland, Ohio, USA.; Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.; Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan., Morita-Nakagawa M; Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.; Oral Medicine Research Centre, Fukuoka Dental College, Fukuoka, Japan., Datta S; Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA., Pavicic PG Jr; Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA., Hamilton TA; Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA., Abu-Elmagd K; Department of General Surgery, Digestive Disease & Surgery Institute, Cleveland Clinic, Cleveland, Ohio, USA., Fujiki M; Department of General Surgery, Digestive Disease & Surgery Institute, Cleveland Clinic, Cleveland, Ohio, USA., Osman M; Department of General Surgery, Digestive Disease & Surgery Institute, Cleveland Clinic, Cleveland, Ohio, USA., D'Amico G; Department of General Surgery, Digestive Disease & Surgery Institute, Cleveland Clinic, Cleveland, Ohio, USA., Eguchi S; Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan., Hashimoto K; Department of General Surgery, Digestive Disease & Surgery Institute, Cleveland Clinic, Cleveland, Ohio, USA.; Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA. |
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Jazyk: | angličtina |
Zdroj: | American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons [Am J Transplant] 2022 Mar; Vol. 22 (3), pp. 955-965. Date of Electronic Publication: 2021 Nov 03. |
DOI: | 10.1111/ajt.16873 |
Abstrakt: | The importance of PD-1/PD-L1 interaction to alloimmune response is unknown in intestinal transplantation. We tested whether PD-L1 regulates allograft tissue injury in murine intestinal transplantation. PD-L1 expression was observed on the endothelium and immune cells in the intestinal allograft. Monoclonal antibody treatment against PD-L1 led to accelerated allograft tissue damage, characterized by severe cellular infiltrations, massive destruction of villi, and increased crypt apoptosis in the graft. Interestingly, PD-L1 -/- allografts were more severely rejected than wild-type allografts, but the presence or absence of PD-L1 in recipients did not affect the degree of allograft injury. PD-L1 -/- allografts showed increased infiltrating Ly6G + and CD11b + cells in lamina propria on day 4, whereas the degree of CD4 + or CD8 + T cell infiltration was comparable to wild-type allografts. Gene expression analysis revealed that PD-L1 -/- allografts had increased mRNA expressions of Cxcr2, S100a8/9, Nox1, IL1rL1, IL1r2, and Nos2 in the lamina propria cells on day 4. Taken together, study results suggest that PD-L1 expression in the intestinal allograft, but not in the recipient, plays a critical role in mitigating allograft tissue damage in the early phase after transplantation. The PD-1/PD-L1 interaction may contribute to immune regulation of the intestinal allograft via the innate immune system. (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.) |
Databáze: | MEDLINE |
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