髓系细胞对于铁和免疫稳态至关重要。铁蛋白重链（FTH1）对于细胞内铁储存至关重要。髓系 FTH1 在许多炎症性疾病的发病机制中起着重要作用。然而，髓系 FTH1 在结肠炎和结肠相关癌症中的作用尚未确定。髓系 FTH1 缺陷和野生型小鼠接受硫酸葡聚糖（DSS）或氮芥-硫酸葡聚糖（AOM-DSS）的治疗，以比较它们对急性结肠炎或结肠相关癌症的易感性。给高铁饮食的髓系 FTH1 缺陷小鼠比野生型小鼠更不容易患上 DSS 诱导的急性结肠炎。机制研究表明，髓系 FTH1 缺陷导致结肠组织中铁摄取蛋白双价金属转运蛋白 1（DMT1）和活性磷酸化信号转导子与转录激活因子 3（STAT3）的表达下降。我们的研究还表明，药物治疗可以恢复髓系 FTH1 缺陷小鼠对 DSS 诱导的急性结肠炎的易感性。一致地，给高铁饮食的髓系 FTH1 缺陷小鼠结肠组织中的 DMT1、磷酸化 STAT3 和炎症减轻，他们更不容易患上结肠相关的结肠癌。我们的研究证明，髓系 FTH1 在过高铁状况下维持 DMT1-铁-STAT3 信号通路激活，从而在结肠炎和结肠相关结肠癌中发挥重要作用。© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Myeloid cells are critical for iron and immune homeostasis. Ferritin heavy chain (FTH1) is essential for intracellular iron storage. Myeloid FTH1 is important in the pathogenesis of many inflammatory diseases. However, the role of myeloid FTH1 in colitis and colitis-associated cancer has not been determined.Myeloid FTH1 deficient and wild-type mice were treated with dextran sodium sulfate (DSS) or azoxymethane (AOM)-DSS to compare their susceptibility to acute colitis or colitis-associated cancer.Myeloid FTH1-deficient mice fed with a high-iron diet were less susceptible to DSS-induced acute colitis than wild type mice. Mechanistic studies showed that myeloid FTH1 deficiency resulted in lower expression of an iron uptake protein divalent metal transporter 1 (DMT1) and active phosphorylated signal transducer and activator of transcription 3 (STAT3) in the colon tissues. Our studies also showed that pharmacological STAT3 reactivation restored the susceptibility of myeloid FTH1-deficient mice to DSS-induced acute colitis. Consistently, myeloid FTH1-deficient mice fed with a high-iron diet had reduced DMT1, phosphorylated STAT3 and inflammation in their colon tissues, and were less susceptible to colitis-associated colorectal cancer.Our study demonstrated that myeloid FTH1 is required for colitis and colitis-associated colorectal cancer via maintaining of DMT1-iron-STAT3 signaling activation under excess iron condition.© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.