期刊
AMERICAN JOURNAL OF TRANSPLANTATION
卷 22, 期 3, 页码 955-965出版社
WILEY
DOI: 10.1111/ajt.16873
关键词
animal models; murine; basic (laboratory) research; science; immune regulation; intestine; multivisceral transplantation; rejection; acute
资金
- Uehara Memorial Foundation
- Japanese Society of Gastroenterology
- Research Program Committee, Cleveland Clinic [RPC 2011-1015]
The study found that the expression of PD-L1 in the intestinal allograft plays a critical role in mitigating allograft tissue damage, while the presence of PD-L1 in the recipient does not affect the degree of allograft injury.
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.
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