Inflammation is a critical player in the development and progression of colon cancer. Basic leucine zipper transcription factor ATF-like 3 (BATF3) plays an important role in infection and tumor immunity through regulating the development of conventional type 1 dendritic cells (cDC1s). However, the function of BATF3 in colitis and colitis-associated colon cancer (CAC) remains unclear. Here, BATF3 wild-type and knockout mice were used to construct an AOM/DSS-induced CAC model. In addition, DSS-induced chronic colitis, bone marrow cross-transfusion (BMT), neutrophil knockout, and other animal models were used for in-depth research. We found that BATF3 deficiency in intestinal epithelial cells rather than in cDC1s inhibited CAC, which was depended on inflammatory stimulation. Mechanistically, BATF3 directly promoted transcription of CXCL5 by forming a heterodimer with JunD, and accelerated the recruitment of neutrophils through the CXCL5-CXCR2 axis, ultimately increasing the occurrence and development of CAC. Tissue microarray and TCGA data also indicated that high expression of BATF3 was positively correlated with poor prognosis of colorectal cancer and other inflammation-related tumors. In summary, our results demonstrate that intestinal epithelial-derived BATF3 relies on inflammatory stimulation to promote CAC, and BATF3 is expected to be a novel diagnostic indicator for colitis and CAC.

炎症是结肠癌发生和发展的关键因素。碱性亮氨酸拉链转录因子 ATF 样 3 (BATF3) 通过调节常规 1 型树突状细胞 (cDC1s) 的发育在感染和肿瘤免疫中发挥重要作用。然而，BATF3 在结肠炎和结肠炎相关结肠癌 (CAC) 中的功能仍不清楚。在这里，BATF3 野生型和敲除小鼠用于构建 AOM/DSS 诱导的 CAC 模型。此外，还利用DSS诱导的慢性结肠炎、骨髓交叉输血（BMT）、中性粒细胞敲除等动物模型进行了深入研究。我们发现肠上皮细胞中的 BATF3 缺陷而不是 cDC1s 中的 BATF3 缺陷抑制了依赖于炎症刺激的 CAC。从机械上讲，BATF3通过与JunD形成异二聚体直接促进CXCL5的转录，并通过CXCL5-CXCR2轴加速中性粒细胞的募集，最终促进CAC的发生和发展。组织微阵列和 TCGA 数据也表明，BATF3 的高表达与结直肠癌和其他炎症相关肿瘤的不良预后呈正相关。总之，我们的研究结果表明，肠上皮来源的 BATF3 依赖于炎症刺激来促进 CAC，BATF3 有望成为结肠炎和 CAC 的新型诊断指标。组织微阵列和 TCGA 数据也表明，BATF3 的高表达与结直肠癌和其他炎症相关肿瘤的不良预后呈正相关。总之，我们的研究结果表明，肠上皮来源的 BATF3 依赖于炎症刺激来促进 CAC，BATF3 有望成为结肠炎和 CAC 的新型诊断指标。组织微阵列和 TCGA 数据也表明，BATF3 的高表达与结直肠癌和其他炎症相关肿瘤的不良预后呈正相关。总之，我们的研究结果表明，肠上皮来源的 BATF3 依赖于炎症刺激来促进 CAC，BATF3 有望成为结肠炎和 CAC 的新型诊断指标。