化疗中白细胞介素-23/白细胞介素-22轴对5-氟尿嘧啶诱导的肠道损伤的调节

IF 4.8 2区医学 Q2 IMMUNOLOGY

International immunopharmacology Pub Date : 2025-02-06 DOI:10.1016/j.intimp.2025.114044

Yongquan Han , Jingping Xu , Yuxuan Zhang , Junqi Sun , Yan Huang , Fang Cai , Yunxiang Ji , Long Zhang , Yezhong Wang

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引用次数: 0

摘要

5-氟尿嘧啶（5-FU）是胃肠道癌症的主要化疗药物，已知可提高生存率，但也会造成严重的肠道损伤，影响患者的生活质量。本研究探讨IL-23-IL-22轴在调节5- fu诱导的肠道损伤中的作用。我们分析了不同肿瘤消退等级（Tumor Regression Grade， TRG）结肠癌患者的癌旁组织损伤，发现TRG与组织损伤严重程度之间存在直接相关性，表明较高的化疗效果与组织损伤增加有关。在5- fu处理的小鼠模型中，我们观察到严重的肠道损伤和增殖细胞的减少。转录组测序和免疫荧光显示，受损组织中的髓样细胞产生IL-23，激活ILC3s分泌IL-22，促进组织修复和稳态。在缺乏IL-22的小鼠中补充IL-22可显著减轻损伤，强调IL-22/IL-23轴作为减少化疗引起的损伤和增强恢复的治疗靶点的潜力。这项研究促进了对化疗生化反应的理解，并为癌症治疗期间维持肠道完整性的治疗提供了新的途径。

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Regulation of 5-fluorouracil-induced intestinal damage by the interleukin-23/interleukin-22 axis in chemotherapy

5-Fluorouracil (5-FU) is a primary chemotherapeutic agent for gastrointestinal cancers, known to improve survival but also cause significant intestinal damage, affecting patient quality of life. This study investigated the IL-23-IL-22 axis’s role in moderating 5-FU-induced intestinal damage. We analyzed paracancerous tissue damage in colon cancer patients with different Tumor Regression Grade (TRG) and found a direct correlation between TRG and tissue damage severity, indicating that higher chemotherapy effectiveness is linked to increased tissue damage. In a 5-FU-treated mouse model, we observed severe intestinal damage and a reduction in proliferative cells. Transcriptome sequencing and immunofluorescence revealed that myeloid cells in damaged tissues produced IL-23, which activated ILC3s to secrete IL-22, promoting tissue repair and homeostasis. IL-22 supplementation in deficient mice significantly mitigated damage, underscoring the IL-22/IL-23 axis’s potential as a therapeutic target to reduce chemotherapy-induced damage and enhance recovery. This research advances understanding of the biochemical responses to chemotherapy and suggests new avenues for developing therapies to maintain intestinal integrity during cancer treatment.

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来源期刊

International immunopharmacology 医学-免疫学

CiteScore

8.40

自引率

3.60%

发文量

935

审稿时长

53 days

期刊介绍： International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.