TNFα是TNF超家族中重要的细胞因子之一，在免疫调节、体内平衡以及发病机制中发挥多效作用。但其对鱼类肠道粘膜免疫的免疫调节作用尚不清楚。在本研究中，我们旨在研究TNFα1在白鲫鱼（WCC）中肠中的免疫调节作用。 WCC-TNFα1序列及其推导的结构首次在WCC中被鉴定。然后，组织特异性分析表明，在鳃中检测到高水平的 WCC-TNFα1 表达。嗜水气单胞菌和脂多糖（LPS）刺激后，在免疫相关组织和培养鱼细胞中分别检测到WCC-TNFα1表达增加的趋势。用 WCC-TNFα1 融合蛋白进行 WCC 肛门插管显示受损绒毛中水肿和模糊外观的增加，以及杯状细胞 (GC) 的萎缩和减少。此外，紧密连接（TJ）基因和粘蛋白基因的表达水平始终低于对照（P<0.05）。 WCC-TNFα1处理可急剧降低中肠的抗氧化状态，而半胱天冬酶（CASP）基因、未折叠蛋白反应（UPR）基因和氧化还原反应基因的表达水平显着增加。我们的结果表明，WCC-TNFα1 可能对 WCC 中肠的抗氧化和粘膜免疫调节产生不利影响。版权所有 © 2023 Elsevier B.V. 保留所有权利。

TNFα is one of important cytokines belonging to TNF superfamily, which can exhibit a pleiotropic effect in immune modulation, homeostasis as well as pathogenesis. However, its immunoregulatory function on mucosal immunity in fish gut are still unclear. In this study, we aimed to investigated the immunoregulatory role of TNFα1 in midgut of white crucian carp (WCC). WCC-TNFα1 sequence and its deduced structure were firstly identified in WCC. Then, tissue-specific analysis revealed that high-level WCC-TNFα1 expression was detected in gill. After Aeromonas hydrophila and lipopolysaccharide (LPS) stimulated, increased trends of WCC-TNFα1 expressions were detected in immune-related tissues and cultured fish cells, respectively. WCC anal-intubated with WCC-TNFα1 fusion protein showed the increased levels of edema and fuzzy appearance in impaired villi, along with atrophy and reduction of goblet cells (GC). Moreover, the expression levels of tight junction (TJ) genes and mucin genes were consistently lower than those of the control (P < 0.05). WCC-TNFα1 treatment could sharply decrease antioxidant status in midgut, while the expression levels of caspase (CASP) genes, unfolded protein response (UPR) genes and redox response genes increased dramatically. Our results suggested that WCC-TNFα1 could exhibit a detrimental effect on antioxidant and mucosal immune regulation in midgut of WCC.Copyright © 2023 Elsevier B.V. All rights reserved.