虽然嗜中性粒细胞在肿瘤中的作用和机制已经得到广泛研究，但芳香族羟基酸受体核转运蛋白（ARNT）对嗜中性粒细胞的确切影响仍不清楚。在本研究中，我们调查了ARNT在CD11b+Gr1+ 嗜中性粒细胞在结肠炎相关结直肠癌中的功能。在本研究中，我们使用了野生型（WT）、ARNT粒细胞特异性缺失小鼠和结肠炎相关结直肠癌小鼠模型。流式细胞仪和共聚焦显微镜评估了CD11b+Gr1+细胞的水平和功能。我们发现，ARNT缺乏促进粒细胞的招募、粒细胞外陷阱（NET）的发展、炎性细胞因子的分泌和抑制活性，当细胞从骨髓进入外周进行结直肠肿瘤发生。 ARNT缺乏在粒细胞中显示出与芳香族羟基酸受体（AHR）缺乏类似的效果。CXCR2是NET发展、细胞因子产生和粒细胞招募所必需的，但不是由Arnt-/-在结直肠癌中诱导的抑制活性。肠道微生物群落对Arnt-/-嗜中性粒细胞的功能改变至关重要，以促进结直肠癌的生长。Arnt-/-嗜中性粒细胞对结直肠癌的影响可通过小鼠共居或抗生素治疗显著恢复。Arnt-/-小鼠粪便的胃内给药表现出与其结直肠癌效应相似的表型。我们的结果定义了转录因子ARNT在调节嗜中性粒细胞招募和功能以及肠道微生物群落中的新角色，对于未来结直肠癌的肠道微生物群落和免疫治疗方法的组合具有重要意义。 © 2023. 作者（们）。

Although the role and mechanism of neutrophils in tumors have been widely studied, the precise effects of aryl hydrocarbon receptor nuclear translocator (ARNT) on neutrophils remain unclear. In this study, we investigated the roles of ARNT in the function of CD11b+Gr1+ neutrophils in colitis-associated colorectal cancer.Wild-type (WT), ARNT myeloid-specific deficient mice and a colitis-associated colorectal cancer mouse model were used in this study. The level and functions of CD11b+Gr1+ cells were evaluated by flow cytometry and confocal microscopy.We found that ARNT deficiency drives neutrophils recruitment, neutrophil extracellular trap (NET) development, inflammatory cytokine secretion and suppressive activities when cells enter the periphery from bone marrow upon colorectal tumorigenesis. ARNT deficiency displays similar effects to aryl hydrocarbon receptor (AHR) deficiency in neutrophils. CXCR2 is required for NET development, cytokine production and recruitment of neutrophils but not the suppressive activities induced by Arnt-/- in colorectal cancer. The gut microbiota is essential for functional alterations in Arnt-/- neutrophils to promote colorectal cancer growth. The colorectal cancer effects of Arnt-/- neutrophils were significantly restored by mouse cohousing or antibiotic treatment. Intragastric administration of the feces of Arnt-/- mice phenocopied their colorectal cancer effects.Our results defined a new role for the transcription factor ARNT in regulating neutrophils recruitment and function and the gut microbiota with implications for the future combination of gut microbiota and immunotherapy approaches in colorectal cancer.© 2023. The Author(s).