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However, the mechanism of its protective effect on target cells and its role on tumour recurrence and interaction with anti\u2010tumour immune checkpoint inhibitors, such as PD\u2010L1 blocking, are still unclear. Here, in a murine heart transplantation model, we observed the upregulation of programmed death\u2010ligand 1 (PD\u2010L1) expression by FK506 in both dendritic cells (DCs) and allografts. Blocking PD\u2010L1 during FK506 treatment increased IFN\u2010\u03b3 and TNF\u2010\u03b1 expression, enhanced CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T cell proliferation, and suppressed Treg differentiation. Moreover, PD\u2010L1 decreased T cell infiltration and induced T cell apoptosis in both the spleen and graft. PD\u2010L1 was not only required in FK506\u2010mediated immunosuppression but also upregulated by FK506. Treatment with SAFit2, a FKBP51 selective inhibitor, reduced the expression of PD\u2010L1 on DCs and the grafts and interfered with the immunosuppressive effect of FK506, suggesting that the mechanism depends on FK506\u2010binding protein (FKBP) 51 expression. Overall, our results add new insights into the role of FK506, not only on T cell cytokine secretion but also on co\u2010inhibitory molecular regulation and target cell immune privilege.<\/jats:p>","DOI":"10.1111\/sji.13203","type":"journal-article","created":{"date-parts":[[2022,7,8]],"date-time":"2022-07-08T11:49:57Z","timestamp":1657280997000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Novel immunosuppressive effect of <scp>FK506<\/scp> by upregulation of <scp>PD\u2010L1<\/scp> via <scp>FKBP51<\/scp> in heart transplantation"],"prefix":"10.1111","volume":"96","author":[{"given":"Xuewei","family":"Luo","sequence":"first","affiliation":[{"name":"Medical College of Guangxi University  Nanning China"},{"name":"Key Laboratory of Functional and Clinical Translational Medicine Fujian Province University, Xiamen Medical College  Xiamen 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