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Blockade or deficiency of PD-L1 expression in intestinal allograft accelerates graft tissue injury in mice.
- Source :
-
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. - Publication Year :
- 2022
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Abstract
- 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 <superscript>-/-</superscript> 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 <superscript>-/-</superscript> allografts showed increased infiltrating Ly6G <superscript>+</superscript> and CD11b <superscript>+</superscript> cells in lamina propria on day 4, whereas the degree of CD4 <superscript>+</superscript> or CD8 <superscript>+</superscript> T cell infiltration was comparable to wild-type allografts. Gene expression analysis revealed that PD-L1 <superscript>-/-</superscript> 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.<br /> (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)
Details
- Language :
- English
- ISSN :
- 1600-6143
- Volume :
- 22
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
- Publication Type :
- Academic Journal
- Accession number :
- 34679256
- Full Text :
- https://doi.org/10.1111/ajt.16873