Alterations in intestinal function play a crucial role in the pathogenesis of sepsis, and the repair of the intestinal barrier is a potential strategy for the treatment of sepsis. Sestrin2 (SESN2), a highly conserved stress-responsive protein, can be induced in response to stress.This paper aimed to explore the role and mechanism of SESN2 in septic intestinal dysfunction.Blood samples were collected from patients with septic intestinal dysfunction, and Caco-2 cells were subjected to lipopolysaccharide (LPS) to construct in vitro models. The expression level of SESN2 was determined in the blood samples and cells. The impacts of SESN2 overexpression on cell inflammation, oxidative stress, barrier integrity, and MAPK/Nrf2 signaling were evaluated. To determine the mediated role of MAPK signaling and ferroptosis, AMPK inhibitor (Compound C) and ferroptosis inducer (erastin) were separately used to treat cells, and the influences on the above aspects in cells were assessed.The expression level of SESN2 was down-regulated in patients with septic intestinal dysfunction and LPS-induced cells. SESN2 overexpression was found to suppress cell inflammation and oxidative stress, maintain barrier integrity, and activate AMPK/Nrf2 signaling. Following the AMPK signaling was inhibited or the ferroptosis was triggered, the effects of SESN2 overexpression on the cells were both reversed.Reduced SESN2 contributed to inflammatory response and barrier dysfunction in septic intestinal dysfunction by promoting ferroptosis via activating the AMPK/Nrf2 signaling pathway.

Wei Liu

Chanchan Xu

Zhiqiang Zou

Qinyong Weng

Ying Xiao

Immunopharmacology and Immunotoxicology

免疫药理学和免疫毒理学杂志致力于针对免疫系统的临床前和临床药物发现和开发。研究涉及各种化合物（包括小分子药物和生物制剂）对免疫活性细胞和免疫反应的免疫调节作用，以及异生物质和药物的免疫毒性。该杂志只对描述特定化合物（而非提取物）机制的研究感兴趣。该杂志将优先考虑慢性炎症、过敏、自身免疫、癌症等疾病的免疫治疗的临床前和临床研究。小药的作用、针对中枢免疫靶点的疫苗和生物制剂以及基于细胞的疗法，包括树突状细胞疗法、T 细胞过继转移和干细胞疗法，是特别令人感兴趣的主题。指向免疫系统内潜在新药靶点或免疫药理学药物开发新技术的出版物也受到欢迎。免疫科学专注于药物开发、免疫治疗和毒理学，该期刊将涵盖感染、过敏、炎症、肿瘤免疫学、退行性疾病、免疫缺陷、神经病学、动脉粥样硬化等。免疫药理学和免疫毒理学将接受原始手稿、简短交流、评论、小型评论、评论、临床试验和临床案例，条件是报告的结果基于原始、临床、或未以任何语言在任何期刊的其他地方发表的基础研究（与科学会议和专题讨论会交流的论文有关的摘要形式除外）。

The journal "Immunopharmacology and Immunotoxicology" focuses on preclinical and clinical drug discovery and development related to the immune system. Research topics include the immunomodulatory effects of various compounds (including small molecules and biologics) on immune-active cells and immune responses, as well as the immunotoxicity of exogenous substances and drugs. The journal is particularly interested in studies that describe the mechanisms of specific compounds (rather than extracts) and prioritizes preclinical and clinical research on immunotherapy for diseases such as chronic inflammation, allergies, autoimmune disorders, and cancer. Topics of special interest include the effects of small molecules, vaccines and biologics targeting central immune pathways, and cell-based therapies, including dendritic cell therapy, T cell adoptive transfer, and stem cell therapy. Publications pointing to potential new drug targets within the immune system or novel techniques for immunopharmacological drug development are also welcomed. The journal covers areas such as infection, allergy, inflammation, tumor immunology, degenerative diseases, immunodeficiency, neurology, and atherosclerosis. "Immunopharmacology and Immunotoxicology" accepts original manuscripts, brief communications, reviews, mini-reviews, clinical trials, and clinical case reports, provided that the reported results are based on original, clinical, or unpublished basic research in any language (excluding abstracts related to papers presented at scientific meetings and symposia).

《Immunopharmacology and Immunotoxicology》致力于免疫系统相关的临床前和临床药物发现与开发。研究内容涵盖各种化合物（包括小分子药物和生物制剂）对免疫活性细胞及免疫反应的调节作用，以及外源性物质和药物的免疫毒性。该期刊特别关注描述特定化合物（而非提取物）机制的研究，优先考虑慢性炎症、过敏、自身免疫、癌症等疾病的免疫治疗相关的临床前和临床研究。小分子药物的作用、针对中枢免疫靶点的疫苗与生物制剂，以及基于细胞的疗法（如树突状细胞疗法、T细胞过继转移和干细胞疗法）是特别感兴趣的主题。此外，指向免疫系统内潜在新药靶点或免疫药理学药物开发新技术的研究也受到欢迎。该期刊涵盖感染、过敏、炎症、肿瘤免疫学、退行性疾病、免疫缺陷、神经病学、动脉粥样硬化等领域。期刊接受原始手稿、简短交流、评论、小型评论、临床试验和临床案例，前提是报告的结果基于原始、临床或未在任何语言的其他期刊上发表的基础研究（与科学会议和专题讨论会交流的论文摘要形式除外）。

Sestrin2 suppresses ferroptosis to alleviate septic intestinal inflammation and barrier dysfunction

Reduced SESN2 contributed to inflammatory response and barrier dysfunction in septic intestinal dysfunction by promoting ferroptosis via activating the AMPK/Nrf2 signaling pathway.

Category	Quartile
医学	4
医学, 毒理学	3
医学, 免疫学	4
医学, 药学	4

Sestrin2 suppresses ferroptosis to alleviate septic intestinal inflammation and barrier dysfunction

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