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‐like 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 nM after stimulation with interleukin‐6 (IL‐6), and the expression of factors associated with the nuclear factor of activated T cells (NFAT)‐BATF/JUN/IRF4 and IL‐21 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‐cell lymphoma 6 (Bcl‐6) and IL‐6 expression in Tfh cells. In addition, Tac inhibited the expression of the BATF/JUN/IRF4 complex, Bcl‐6 and IL‐21 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‐BATF/JUN/IRF4‐IL‐21 axis, and the BATF/JUN/IRF4 complex participates in the inhibition of IL‐21‐producing Tfh cells after treatment with Tac. These findings suggest that the BATF/JUN/IRF4 complex–IL‐21 axis may be used as a potential target for attenuating rejection injury after LTx.

中文翻译：

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BATF/JUN/IRF4复合物在他克莫司介导的肝移植后急性排斥反应中Tfh细胞免疫抑制中的作用。

排斥损伤是肝移植（LTx）后的严重并发症。他克莫司 (Tac) 是预防移植后肝排斥反应的关键免疫抑制剂。碱性亮氨酸拉链 ATF 样转录因子 (BATF)/JUN/干扰素调节因子 4 (IRF4) 复合物在免疫反应中发挥关键作用。本研究旨在探讨 BATF/JUN/IRF4 复合物在用 Tac 治疗 LTx 后排斥反应中的作用。在此，DA和Lewis（LEW）大鼠用于构建LTx动物模型。接受者 LEW 大鼠用 Tac 或盐水进行皮下治疗。用白细胞介素-6 (IL-6) 刺激后，用 1 和 10 nM 的 Tac 处理脾单核细胞，与活化 T 细胞核因子 (NFAT)-BATF/JUN/IRF4 和 IL- 相关因子的表达检测到 21 个。结果表明，Tac 延长了同种异体移植物的存活时间，减轻了炎症损伤，降低了外周血单核细胞中 T 滤泡辅助 (Tfh) 细胞的百分比频率，并抑制了 B 细胞淋巴瘤 6 (Bcl-6) 和 IL-6 的表达。 Tfh 细胞。此外，Tac 抑制 BATF/JUN/IRF4 复合物的表达，Bcl-6 和 IL-21 NFATc1 和 NFATc2 被 Tac 抑制，并与 BATF 和 IRF4 的启动子相互作用。总之，排斥损伤的减弱可能依赖于 NFAT-BATF/JUN/IRF4-IL-21 轴，并且 BATF/JUN/IRF4 复合物参与了 Tac 处理后对产生 IL-21 的 Tfh 细胞的抑制. 这些发现表明 BATF/JUN/IRF4 复合物-IL-21 轴可用作减轻 LTx 后排斥损伤的潜在靶标。