{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T14:33:10Z","timestamp":1780583590195,"version":"3.54.1"},"reference-count":25,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,8,4]],"date-time":"2020-08-04T00:00:00Z","timestamp":1596499200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81370573"],"award-info":[{"award-number":["81370573"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Rejection injury is a serious complication after liver transplantation (LTx). Tacrolimus (Tac) is a key immunosuppressive agent in the prevention of liver rejection after transplantation. The basic leucine zipper ATF\u2010like transcription factor (BATF)\/JUN\/interferon regulatory factor 4 (IRF4) complex serves critical functions in the immune response. This study aimed to explore the role of the BATF\/JUN\/IRF4 complex in rejection after LTx by treatment with Tac. Herein, DA and Lewis (LEW) rats were used to construct the LTx animal model. The recipient LEW rats were treated with Tac or saline, subcutaneously. Splenic mononuclear cells were treated with Tac at 1 and 10\u2009nM after stimulation with interleukin\u20106 (IL\u20106), and the expression of factors associated with the nuclear factor of activated T cells (NFAT)\u2010BATF\/JUN\/IRF4 and IL\u201021 were detected. The results demonstrated that Tac prolonged the allografts survival and attenuated inflammation injury, and decreased the percentage frequencies of T follicular helper (Tfh) cells in peripheral blood mononuclear cells and inhibited B\u2010cell lymphoma 6 (Bcl\u20106) and IL\u20106 expression in Tfh cells. In addition, Tac inhibited the expression of the BATF\/JUN\/IRF4 complex, Bcl\u20106 and IL\u201021 NFATc1 and NFATc2 were inhibited by Tac, and interacted with the promoter of BATF and IRF4. In conclusion, the attenuation of rejection injury may be dependent on the NFAT\u2010BATF\/JUN\/IRF4\u2010IL\u201021 axis, and the BATF\/JUN\/IRF4 complex participates in the inhibition of IL\u201021\u2010producing Tfh cells after treatment with Tac. These findings suggest that the BATF\/JUN\/IRF4 complex\u2013IL\u201021 axis may be used as a potential target for attenuating rejection injury after LTx.<\/jats:p>","DOI":"10.1002\/jcp.29953","type":"journal-article","created":{"date-parts":[[2020,8,4]],"date-time":"2020-08-04T15:02:55Z","timestamp":1596553375000},"page":"1776-1786","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Roles of BATF\/JUN\/IRF4 complex in tacrolimus mediated immunosuppression on Tfh cells in acute rejection after liver transplantation"],"prefix":"10.1002","volume":"236","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7734-1143","authenticated-orcid":false,"given":"Tengqian","family":"Tang","sequence":"first","affiliation":[{"name":"The Institute of Hepatobiliary Surgery, Southwest Hospital, Army Medical University  Chongqing 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