International immunopharmacology最新文献

{"title":"Exploring the role of Mitoferrin-1 in Ferroptosis and mitochondrial damage in acute ischemic stroke","authors":"Ruijia You,&nbsp;Bin Sun,&nbsp;Jing Luo,&nbsp;Nan Shao,&nbsp;Wenwen Si","doi":"10.1016/j.intimp.2025.114625","DOIUrl":"10.1016/j.intimp.2025.114625","url":null,"abstract":"<div><div>The pathogenesis of acute ischemic stroke (AIS) is complex, with limited therapeutic options available during the acute phase. Therefore, investigating the underlying mechanisms of AIS is critical. Ferroptosis has been implicated in AIS-induced damage; however, its precise molecular mechanisms remain elusive. In this study, we explored the role of Mitoferrin-1 (Mfrn1) in AIS using a combination of in vitro and in vivo models, including RNA sequencing, RNA interference (RNAi), Adeno-associated virus (AAV9) injection, gene overexpression, and ferroptosis detection. Our results demonstrated that Mfrn1 expression, mitochondrial iron levels, mitochondrial injury, and ferroptosis were significantly increased in AIS models. Knockdown of Mfrn1 attenuated ferroptosis and oxygen-glucose deprivation/reperfusion (OGD/R)-induced injury, whereas overexpression of Mfrn1 had the opposite effect. Similarly, silencing Mfrn1 decreased mitochondrial iron accumulation and injury, while its overexpression exacerbated both. In middle cerebral artery occlusion/reperfusion (MCAO/R) rats, silencing Mfrn1 suppressed ferroptosis, reduced AIS-related injury, lowered mitochondrial iron levels, and mitigated mitochondrial damage. These findings suggest that Mfrn1 exacerbates AIS damage by promoting mitochondrial iron accumulation and injury. This study highlights Mfrn1 as a potential therapeutic target for AIS.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"155 ","pages":"Article 114625"},"PeriodicalIF":4.8,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Urolithin a attenuates rheumatoid arthritis by inhibiting inflammation and pyroptosis in fibroblasts via the AMPK/ NF-κB signaling pathway","authors":"Hao Chen ,&nbsp;Zhen Zhang ,&nbsp;Congcong Lu ,&nbsp;Yi Ding ,&nbsp;Zhengao Huang ,&nbsp;Maoqiang Li ,&nbsp;Liulong Zhu","doi":"10.1016/j.intimp.2025.114604","DOIUrl":"10.1016/j.intimp.2025.114604","url":null,"abstract":"<div><div>Urolithin A (UA), a metabolite of natural polyphenols produced by the gut microbiota, alleviates the symptoms of rheumatoid arthritis (RA) by inhibiting the inflammatory response. UA alleviates the clinical symptoms of RA by inhibiting the occurrence of an inflammatory response, but the specific regulatory mechanism remains unclear. In this study, we established a CIA model in 8-week-old DBA mice and chose LPS-stimulated NIH/3 T3 cells to explore the effects of UA and attempted to elucidate its potential mechanisms. Our results showed UA significantly reduced arthritis scores, and inhibited inflammation, pannus formation, and cartilage and bone destruction of inflamed joints in CIA mice. In vitro, UA inhibited LPS-induced migration and proliferation, and alleviated NLRP3-mediated pyroptosis, significantly inhibiting the protein expression levels of NLRP3, N-terminal gasdermin D, interleukin-1β, caspase-1, and ASC in NIH/3T3 cells. A mechanistic investigation revealed that LPS enhanced phosphorylation of NF-κB and downregulated that of AMPK, which were categorically counteracted by UA treatment. Therefore, UA represents a new class of promising RA treatments targeting fibroblasts, widening the therapeutic options for RA.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"155 ","pages":"Article 114604"},"PeriodicalIF":4.8,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel anti-PD-L1 DNA aptamer, Apta35 enhances non-small cell lung cancer cell cytotoxicity and apoptosis through lung cancer-activated T lymphocytes","authors":"Priyatharcini Kejamurthy,&nbsp;Jaganathan MK,&nbsp;Ramya Devi KT","doi":"10.1016/j.intimp.2025.114621","DOIUrl":"10.1016/j.intimp.2025.114621","url":null,"abstract":"<div><div>The prevalence of Programmed death ligand 1 (PD-L1) expression in the population of NSCLC patients and blocking the PD1/PD-L1 pathway by inhibiting the PD-1 receptor on immune cells or the PD-L1 ligand on tumour and/or immune cells can inhibit tumour growth. EFBALite algorithm that enables efficient and cost-effective selection of aptamers, expediting the process. Here, we present the development, computational validation, and <em>in vitro</em> analysis of NSCLC of DNA aptamers targeting PD-L1. The Gibbs free energy of two anti-PD-L1 aptamers, <em>Apta35</em> and <em>Apta90</em> with −3.06 and − 2.4 kcal/mol respectively. The docking score for Apta35 was −272.3 and 1171.765 for HDOCK and ZDOCK respectively. Further, the Apta35 was taken for the <em>in vitro</em> studies as it was more stable and incubated with NCI-H460. Initially, we confirmed the binding of the TAMRA-labelled Apta35 to the NCI-H460 cell surface through microscopic imaging and further confirmed through FACS analysis. Further experimental results showed that the Apta35 treated along with the act-T cells group reduced the percentage of viability (28 ± 3.5), increased toxicity, and reduced count of NCI-H460 cells when compared with the cells treated only with the act-T cells concerning the treatment to 50 nM concentration. In summary, targeting PD-L1 with a specific aptamer provides an innovative strategy for targeting NSCLC. Apta35 aptamer showed no significant toxicity in the BALB/c nude mice while it was injected every 2 days for a total of 12 days of treatment.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"155 ","pages":"Article 114621"},"PeriodicalIF":4.8,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sotagliflozin provides additional benefits for high-fat diet-induced cardiac inflammatory injury by extra inhibiting P38MAPK and JNK","authors":"Jian-chao Luo ,&nbsp;Le-hao Jin ,&nbsp;Yun-shan Zhong ,&nbsp;Xiao-yu Xu ,&nbsp;Zhe-yan Zhang ,&nbsp;Jing Chen ,&nbsp;Zhong-xi Chen ,&nbsp;Sen Li ,&nbsp;Xiao-dan Zhang ,&nbsp;Jian-chang Qian","doi":"10.1016/j.intimp.2025.114631","DOIUrl":"10.1016/j.intimp.2025.114631","url":null,"abstract":"<div><div>SGLT1/2 dual-target inhibitors have demonstrated significant benefits for diabetic patients, particularly those with cardiovascular complications. However, pharmacological mechanisms beyond SGLT1/2 inhibition remain incompletely understood. The current study investigated the effects of sotagliflozin, a representative SGLT1/2 inhibitor, on obesity-related cardiomyopathy and explored the underlying molecular mechanisms. A high-fat diet-induced obese mouse model was employed to evaluate cardiac function and biochemical parameters, complemented by transcriptomic analysis and network pharmacology to identify potential therapeutic targets. Results demonstrated that sotagliflozin effectively ameliorated hyperglycemia, hyperlipidemia, and hypertension in obese mice while significantly improving obesity-induced cardiac dysfunction through suppression of myocardial inflammatory responses. Transcriptomic analysis revealed enrichment of differentially expressed genes in the MAPK pathway, which was further corroborated by network pharmacology. Both in vivo and in vitro validation confirmed direct binding of sotagliflozin to P38MAPK and JNK, leading to significant inhibition of their activation induced by palmitic acid or high-fat diet. These findings suggest that the cardioprotective effects of sotagliflozin against obesity-related cardiomyopathy are mediated through multi-target inhibition of P38MAPK and JNK pathways. Targeting inflammatory signaling pathways while managing cardiovascular risk factors may represent a promising therapeutic strategy for obesity-associated cardiovascular diseases.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"155 ","pages":"Article 114631"},"PeriodicalIF":4.8,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nicotinamide mononucleotide ameliorates hypertriglyceridemia pancreatitis via NAD+/SIRT1-mediated TXNIP suppression and NOTCH pathway for accelerated repair-associated processes","authors":"Hongtao Duan ,&nbsp;Rui Zhang ,&nbsp;Aiminuer Asikaer ,&nbsp;Liang Pan ,&nbsp;Shui Wang ,&nbsp;Kuilong Huang ,&nbsp;Deshuai Lou ,&nbsp;Yuanqiang Wang ,&nbsp;Zhihua Lin ,&nbsp;Yan Shen","doi":"10.1016/j.intimp.2025.114620","DOIUrl":"10.1016/j.intimp.2025.114620","url":null,"abstract":"<div><div><strong>Background &amp; Aims:</strong> Acute pancreatitis (AP) is a life-threatening condition, and hypertriglyceridemia (HTG) is recognized as a factor exacerbating AP and impeding pancreatic regeneration. Nicotinamide mononucleotide (NMN), a precursor in the biosynthesis of nicotinamide adenine dinucleotide (NAD⁺), is extensively utilized to restore NAD⁺ levels. However, the impact of NMN on HTG-AP has not been previously addressed, which prompted our investigation into its effects and underlying mechanisms in this study.</div><div><strong>Methods &amp; Results:</strong> Here, through bioinformatics analysis and in vivo experiments, we identified abnormalities in the thioredoxin system. In vitro studies revealed that NMN rescued oleic acid (OA)- and palmitic acid (PA)-induced mitochondrial dysfunction and cellular injury in pancreatic acinar cells by suppressing thioredoxin-interacting protein (TXNIP) through NAD⁺/sirtuin 1 (SIRT1) signaling. Repeated administration of NMN significantly ameliorated P407 and caerulein (CER)-induced pancreatic injury and dysfunction in mice. Consistently, NMN exhibited the potential to reduce inflammatory responses, lower serum lipid levels, and mitigate the accumulation of reactive oxygen species (ROS). More importantly, sustained NMN treatment inhibited the NOTCH pathway and promoted M2-type macrophage dominance during the pancreatic repair phase, influencing early or late macrophage polarization, which significantly enhanced inflammation resolution. As expected, in vitro models using mouse bone marrow-derived macrophage (BMDM), RAW 264.7, and THP-1 cells confirmed that NMN influences macrophage phenotype through the NOTCH pathway.</div><div><strong>Conclusions:</strong> Therefore, NMN ameliorates pancreatic acinar cell injury via NAD⁺/SIRT1-mediated TXNIP suppression and may influence macrophage polarization by inhibiting NOTCH activation, offering a novel therapeutic strategy for the treatment and repair of HTG-AP.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"155 ","pages":"Article 114620"},"PeriodicalIF":4.8,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antiproliferative and apoptotic effects of (1R*,12R*)-dolabella-4(16),7,10-triene-3,13-dione (CI-A) in oral cancer cells are mediated by oxidative stress and ERK activation","authors":"Ya-Ting Chuang ,&nbsp;Wangta Liu ,&nbsp;Tsu-Ming Chien ,&nbsp;Yuan-Bin Cheng ,&nbsp;Jiiang-Huei Jeng ,&nbsp;Ching-Yeu Chen ,&nbsp;Jen-Yang Tang ,&nbsp;Hsueh-Wei Chang","doi":"10.1016/j.intimp.2025.114615","DOIUrl":"10.1016/j.intimp.2025.114615","url":null,"abstract":"<div><div>The anticancer effects and mechanisms of the main component (CI-A) of methanol extracts of <em>Clavularia inflat</em> have not been reported. This study explores the anti-oral cancer effect and mechanism of (1<em>R</em>*,12<em>R</em>*)-dolabella-4(16),7,10-triene-3,13-dione (CI-A) and compared with normal cells. CI-A shows oxidative-stress-dependent preferential antiproliferation of oral cancer cells without normal cell toxicity. CI-A triggers cell cycle dysregulation, apoptosis/caspase activation, cellular/mitochondrial ROS induction, glutathione depletion, and oxidative DNA damage in oral cancer but not normal cells. After testing with three MAPK (p38, JNK, and ERK) inhibitors, only the ERK inhibitor (PD98059) protects against CI-A-induced antiproliferation in oral cancer cells. CI-A upregulates phosphorylated ERK in oral cancer cells compared to normal cells. Notably, a ROS inhibitor, <em>N</em>-acetylcysteine (NAC), attenuates all CI-A-modulated changes. Moreover, the CI-A-triggered annexin V-detected apoptosis and caspase 3/8/9 activations of oral cancer cells were downregulated by PD98059. In conclusion, CI-A induces the oxidative-stress- and ERK-dependent antiproliferative and apoptotic mechanism in oral cancer cells and shows the benefit of non-cytotoxicity to normal cells.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"155 ","pages":"Article 114615"},"PeriodicalIF":4.8,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomal PD-L1 in non-small cell lung Cancer: Implications for immune evasion and resistance to immunotherapy","authors":"Mojtaba Tarin ,&nbsp;Mahsa Akbari Oryani ,&nbsp;Hossein Javid ,&nbsp;Mehdi Karimi-Shahri","doi":"10.1016/j.intimp.2025.114519","DOIUrl":"10.1016/j.intimp.2025.114519","url":null,"abstract":"<div><div>Exosomes, characterized by their bilayer lipid structure, are crucial in mediating intercellular signaling and contributing to various physiological processes. Tumor cells produce distinct exosomes facilitating cancer progression, angiogenesis, and metastasis by conveying signaling molecules. A notable feature of these tumor-derived exosomes is the presence of programmed death-ligand 1 (PD-L1) on their surface. The PD-L1/programmed cell death receptor-1 (PD-1) signaling axis serves as a critical immune checkpoint, enabling tumors to evade immune detection and antitumor activity. The advancement of immunotherapy targeting the PD-1/PD-L1 pathway has significantly impacted the treatment landscape for non-small cell lung cancer (NSCLC). Despite its promise, evidence indicates that many patients experience limited responses or develop resistance to PD-1/PD-L1 inhibitors. Recent studies suggest that exosomal PD-L1 contributes to this resistance by modulating immune responses and tumor adaptability. This study reviews the PD-1/PD-L1 pathway's characteristics, current clinical findings on PD-L1 inhibitors in NSCLC, and exosome-specific attributes, with a particular focus on exosomal PD-L1. Furthermore, it examines the growing body of research investigating the role of exosomal PD-L1 in cancer progression and response to immunotherapy, underscoring its potential as a target for overcoming resistance in NSCLC treatment.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"155 ","pages":"Article 114519"},"PeriodicalIF":4.8,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Urolithin A enhances diabetic wound healing: Insights from parkin-mediated mitophagy in endothelial progenitor cells","authors":"Xia Fang ,&nbsp;Zhenxuan Shao ,&nbsp;Hongfeng Ding ,&nbsp;Haoxiang Xu ,&nbsp;Zhuolong Tu ,&nbsp;Hui Wang ,&nbsp;Dawei Li ,&nbsp;Cheng Huang ,&nbsp;Chang Jiang","doi":"10.1016/j.intimp.2025.114572","DOIUrl":"10.1016/j.intimp.2025.114572","url":null,"abstract":"<div><div>Diabetes is often associated with delayed wound healing, where endothelial progenitor cells (EPCs) play a key role in maintaining vascular integrity and promoting angiogenesis. Urolithin A, a metabolite derived from pomegranates, strawberries, and nuts, has demonstrated therapeutic potential in reversing damage in various disease models, indicating its potential in facilitating diabetic wound healing. In this study, we investigated the effects of Urolithin A on mitochondrial dysfunction, apoptosis, and impaired function in EPCs treated with high glucose. Through sequencing and molecular docking analysis, we found that Urolithin A exerts its therapeutic action by upregulating Parkin and activating mitophagy. Furthermore, Urolithin A alleviated delayed wound healing in diabetic rat models. In conclusion, Urolithin A holds promise as a therapeutic agent for improving diabetes-related delayed wound healing by targeting mitochondrial dysfunction and enhancing EPC function.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"155 ","pages":"Article 114572"},"PeriodicalIF":4.8,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"APOC1 expressed in macrophages promotes the pulmonary metastasis of colorectal cancer via CCL2/CCL5","authors":"Fei Qin ,&nbsp;Haosheng Zheng ,&nbsp;Jiayan Wu ,&nbsp;Zui Liu ,&nbsp;Yuzhen Zheng ,&nbsp;Xingping Yang ,&nbsp;Junguo Chen ,&nbsp;Weihao Deng ,&nbsp;Ziyin Luo ,&nbsp;Jian Tan ,&nbsp;Weijie Cai ,&nbsp;Bozhu Jian ,&nbsp;Yushuai Zeng ,&nbsp;Xianyu Qin ,&nbsp;Hongying Liao","doi":"10.1016/j.intimp.2025.114611","DOIUrl":"10.1016/j.intimp.2025.114611","url":null,"abstract":"<div><div>Metastasis is the main cause of death in colorectal cancer (CRC), and the lungs are common sites of metastasis. However, there is little effective target to intervene colorectal cancer pulmonary metastasis (CCPM), especially on its unique immune microenvironment. In this study, sixteen genes were identified as core CCPM-related differentially expressed genes (DEGs) between CRC and CCPM. Three genes including Apolipoprotein C1 (APOC1) were associated with prognosis, stage and metastasis of CRC. In immunohistochemistry, APOC1 was mainly expressed in macrophages, and expressed more in CCPM than CRC. Patients with synchronous CCPM, higher stage, poorer OS and CCPM-free interval tended to have higher expression. In experiments in vitro, knockdown of APOC1 in macrophages reduced the migration, invasion, and epithelial-mesenchymal transition of CRC cells. Knockdown of APOC1 in macrophages significantly decreased secretion of chemokines like CCL2 and CCL5. The pro-metastatic effect of macrophages expressing APOC1 was partially blocked by the antibodies of CCL2 and CCL5. Activation of STAT3 was a key process in APOC1's regulation of CCL2 and CCL5. In experiments in vivo, knockdown of APOC1 in macrophages reduced pulmonary metastasis. To conclude, APOC1 is one of core CCPM-related DEGs and associated with the metastasis and survival of CRC. Macrophages expressing APOC1 promote the CCPM by APOC1-STAT3-CCL2/CCL5 axis. APOC1 and macrophages expressing APOC1 play vital roles and may be potential therapeutic targets in CCPM.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"154 ","pages":"Article 114611"},"PeriodicalIF":4.8,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143785540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The emerging role of IL-22 as a potential radiosensitivity biomarker for radiation-induced intestinal injury","authors":"Jianyu Wang ,&nbsp;Tonglin Wang ,&nbsp;Lei Zhu ,&nbsp;Junshu Wang ,&nbsp;Qiaohui Gao ,&nbsp;Li Guo ,&nbsp;Ganggang Lv ,&nbsp;Wenle Zhang ,&nbsp;Zefang Zhang ,&nbsp;Changbin Yang ,&nbsp;Lin Yao ,&nbsp;Junye Liu ,&nbsp;Fei Da","doi":"10.1016/j.intimp.2025.114573","DOIUrl":"10.1016/j.intimp.2025.114573","url":null,"abstract":"<div><div>Considering the beneficial role played by IL-22 in alleviating radiation-induced intestinal injury through its promotion of epithelial regeneration, it was hypothesized that individuals with elevated IL-22 levels might display either minimal intestinal injury or increased resistance following ionizing irradiation exposure. To assess the impact of IL-22 on intestinal radiosensitivity, IL-22 expression levels was detected in serum of normal mice. Mice naturally with high or low levels of IL-22 or pretreated with IL-22 or anti-IL-22 were subjected to 10 Gy of total abdominal radiation (TAI). Daily observation, morphometric analysis, quantitative reverse transcriptase polymerase chain reaction, immunohistochemistry and western blot were employed to measure weight loss, survival rate, cell proliferation and death, and DNA damage. Furthermore, influence of IL-22 pretreatment on survival of intestinal organoid exposed to 6 Gy X-rays was evaluated. The results showed that IL-22 expression levels were varied between individuals. Surprisingly, mice with high IL-22 levels displayed exacerbated intestinal injury manifesting as increased weight loss, reduced regeneration capacity and more cell apoptosis. Notably, a strong positive correlation between weight loss and IL-22 expression level was observed. Additionally, pretreatment with IL-22 resulted in increased mortality accompanied by enhanced cell apoptosis and DNA damage in crypt of early exposure, as well as diminished survival of intestinal organoid, while pretreatment with anti-IL-22 antibody alleviated the intestinal injury. In this study, we established a direct link between IL-22 and radiosensitivity, suggesting IL-22 could be used as a potential biomarker for predicting individual intestinal radiosensitivity prior to radiation exposure.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"155 ","pages":"Article 114573"},"PeriodicalIF":4.8,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143785232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}