{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T06:35:21Z","timestamp":1773815721900,"version":"3.50.1"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Long-term immunosuppression following organ transplantation results in an elevated risk of malignancies in recipients, which constitutes a major factor limiting their long-term survival. Therefore, the development of immunosuppressant with anti-tumor efficacy holds critical significance. Icaritin (ICT), a clinically employed antitumor drug, enhances anti tumor immunity by reshaping the tumor immune microenvironment. Moreover, recent evidence highlights its immunomodulatory role in mitigating multiple autoimmune diseases. However, whether ICT can attenuate the allograft rejection remains poorly characterized.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Fully major histocompatibility complex-mismatched heterotopic heart transplantation was conducted from BALB\/c mice to C57BL\/6J mice. The rejection of the allografts was assessed via H&amp;amp;E staining and immunohistochemistry. Single-cell RNA sequencing (scRNA-seq) and flow cytometry were carried out on recipient splenocytes. In vitro, isolated na\u00efve CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells were cultured in Th1-polarizing conditioned medium with various treatments, and flow cytometry and quantitative PCR (qPCR) were employed to delineate the role of the Proviral integration site for Moloney murine leukemia virus (PIM1) during Th1 cell differentiation. Molecular docking, molecular dynamics simulations, and cellular thermal shift assay were employed to demonstrate the binding capacity between ICT and CCAAT\/enhancer-binding protein \u03b2 (CEBPB). A tumor-bearing murine heterotopic heart transplantation model was employed to demonstrate the dual efficacy of ICT in immunosuppression and antitumor.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      ICT markedly attenuated acute cardiac allograft rejection and enhanced graft survival. scRNA-seq and flow cytometric analyses revealed a significant reduction in the proportion of splenic Th1 cells in ICT-treated recipient mice.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , ICT suppressed CD4\n                      <jats:sup>+<\/jats:sup>\n                      T-cell activation, proliferation, and Th1 cell differentiation in a dose-dependent manner. By binding to the transcription factor CEBPB, ICT inhibits PIM1 expression, and thereby suppresses the activation, proliferation, and Th1 differentiation of CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells. In the tumor-bearing murine heart transplantation model, ICT potentiated the immunosuppressive efficacy of tacrolimus while reducing the tumor burden.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      While exerting antitumor effects, ICT attenuates allograft rejection by targeting the CEBPB\/PIM1 axis, thereby suppressing CD4\n                      <jats:sup>+<\/jats:sup>\n                      T-cell activation, proliferation, and Th1 differentiation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1762553","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T05:39:03Z","timestamp":1773812343000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Dual role of icaritin in attenuating 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Shandong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Chen","sequence":"additional","affiliation":[{"name":"Nankai University School of Medicine","place":["Tianjin, China"]},{"name":"Tianjin Organ Transplantation Research Center","place":["Tianjin, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sei","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Institute of Transplantation Medicine, Nankai University","place":["Tianjin, China"]},{"name":"College of Life Sciences, Nankai University","place":["Tianjin, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenzhou","family":"Wu","sequence":"additional","affiliation":[{"name":"Institute of Transplantation Medicine, Nankai University","place":["Tianjin, China"]},{"name":"College of Life Sciences, Nankai University","place":["Tianjin, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Zheng","sequence":"additional","affiliation":[{"name":"Nankai University School of Medicine","place":["Tianjin, China"]},{"name":"Tianjin Organ Transplantation Research Center","place":["Tianjin, China"]},{"name":"Institute of Transplantation Medicine, Nankai University","place":["Tianjin, China"]},{"name":"Tianjin Key Laboratory of Organ Transplantation, Tianjin First Central Hospital","place":["Tianjin, China"]},{"name":"Key Laboratory of Transplant Medicine, Chinese Academy of Medical Science","place":["Tianjin, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongyang","family":"Shen","sequence":"additional","affiliation":[{"name":"Nankai University School of Medicine","place":["Tianjin, China"]},{"name":"Tianjin Organ Transplantation Research Center","place":["Tianjin, China"]},{"name":"Institute of Transplantation Medicine, Nankai University","place":["Tianjin, 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