Inflammation最新文献

Exposure to Dietary Nitrite Exacerbates Lupus in MRL/lpr Mice by Enhancing Integrin Alpha M. 饮食中暴露于亚硝酸盐通过增强整合素α M使MRL/lpr小鼠狼疮恶化。

IF 5 2区医学

Inflammation Pub Date : 2025-08-04 DOI: 10.1007/s10753-025-02347-9

Yiwu Qiu, Qingyi Zhang, Xueting Yang, Chengping Wen, Zhixing He, Mingzhu Wang

{"title":"Exposure to Dietary Nitrite Exacerbates Lupus in MRL/lpr Mice by Enhancing Integrin Alpha M.","authors":"Yiwu Qiu, Qingyi Zhang, Xueting Yang, Chengping Wen, Zhixing He, Mingzhu Wang","doi":"10.1007/s10753-025-02347-9","DOIUrl":"https://doi.org/10.1007/s10753-025-02347-9","url":null,"abstract":"There is a recognized longitudinal association between serum nitrogen oxides levels and disease activity in lupus nephritis. Recently, increased exposure to high levels of nitrite has raised significant concerns, though its impact on lupus pathogenesis has not been fully elucidated. Using the MRL/lpr spontaneous lupus model, we employed integrated immunological and transcriptomic approaches to investigate nitrite's effects. Flow cytometry revealed significant elevations in splenic double negative T (DN T) cells, T follicular helper (Tfh) cells, and plasma cells following nitrite intervention, along with a reduction in splenic regulatory T (Treg) cells. ELISA quantification revealed elevated serum anti-double-stranded DNA antibodies (anti-dsDNA), antinuclear antibodies (ANA), and pro-inflammatory cytokines (IL-12p70, TNF-α), correlating with aggravated renal pathology in nitrite-exposed mice. Transcriptome analysis further revealed significant gene expression changes in both spleen and kidney tissues associated with nitrite exposure. Notably, three KEGG pathways, cell adhesion molecules, osteoclast differentiation, and B cell receptor signaling pathway, were consistently enriched in both the spleen and kidney transcriptomes. Subsequent western blot analysis identified that the Itgam (integrin alpha M)-related cell adhesion molecule pathway potentially mediated the mechanism by which nitrite aggravated lupus in MRL/lpr mice. To explore this mechanism, the integrin antagonist lifitegrast was used to inhibit the expression of Itgam in the nitrite-exposed MRL/lpr mice, resulting in attenuation of nitrite-induced lupus exacerbation. Collectively, these findings suggested that nitrite exposure could aggravate lupus by promoting Itgam expression.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144775326","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}

引用次数: 0

Large Peritoneal Macrophages Promote the Resolution of Inflammation in Injured Endometrium. 巨噬细胞促进损伤子宫内膜炎症的消退。

IF 5 2区医学

Inflammation Pub Date : 2025-08-02 DOI: 10.1007/s10753-025-02335-z

Jingman Li, Lijie Yin, Jiali Wang, Yuchen Pan, Chen Peng, Yue Dong, Sunan Shen, Yayi Hou, Guangfeng Zhao

{"title":"Large Peritoneal Macrophages Promote the Resolution of Inflammation in Injured Endometrium.","authors":"Jingman Li, Lijie Yin, Jiali Wang, Yuchen Pan, Chen Peng, Yue Dong, Sunan Shen, Yayi Hou, Guangfeng Zhao","doi":"10.1007/s10753-025-02335-z","DOIUrl":"https://doi.org/10.1007/s10753-025-02335-z","url":null,"abstract":"Macrophages play a significant role in the repair of endometrial injuries. While large peritoneal macrophages (LPMs) have been reported to migrate to injured organs and repair tissues within the peritoneal cavity, their involvement in the repair of injured endometrium remains unclear. In this study, we utilize a mouse model of endometrial injury that does not involve laparotomy, a procedure that typically results in a substantial loss of LPMs. Strikingly, we find that LPMs reach the endometrium within 6 h post-modeling. By depleting or supplementing LPMs, our results reveal that these cells are capable of engulfing dead cells in the endometrium and resolving inflammation. Additionally, we observe that the migration efficiency of LPMs is enhanced with increased levels of 17β-estradiol (E2) in mice. In vitro assays further confirm that E2 accelerates the migration of LPMs towards apoptotic endometrial stromal cells. Overall, our findings demonstrate that LPMs rapidly migrate into injured endometrium in relation to E2 levels and facilitate the process of tissue repair.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768615","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}

引用次数: 0

The Role of CCL11-CCR3 Induced Mitochondrial Dysfunction and Oxidative Stress in Cognitive Impairment in Early-onset Schizophrenia: Insights from Preclinical Studies. CCL11-CCR3诱导的线粒体功能障碍和氧化应激在早发性精神分裂症认知障碍中的作用：来自临床前研究的见解

IF 5 2区医学

Inflammation Pub Date : 2025-07-28 DOI: 10.1007/s10753-025-02344-y

Xing Luo, Jiangwen Dong, Tao Li

{"title":"The Role of CCL11-CCR3 Induced Mitochondrial Dysfunction and Oxidative Stress in Cognitive Impairment in Early-onset Schizophrenia: Insights from Preclinical Studies.","authors":"Xing Luo, Jiangwen Dong, Tao Li","doi":"10.1007/s10753-025-02344-y","DOIUrl":"https://doi.org/10.1007/s10753-025-02344-y","url":null,"abstract":"Abnormal cytokine expression has been implicated as a potential contributor to neurodegeneration. This study aimed to investigate the plasma cytokine profiles in patients with early-onset schizophrenia (SCZ) and to explore the molecular mechanisms underlying the role of the key cytokine CCL11 in contributing to cognitive impairment. Plasma concentrations of 44 cytokines were quantified in individuals with SCZ. The effects of CCL11 on mitochondrial function were examined in vitro using primary hippocampal neurons. An in vivo model was subsequently developed by administering CCL11 into the lateral ventricle. The impact of the CCL11-CCR3 signaling pathway on mitochondrial function, oxidative stress, and cognitive function within the hippocampus was assessed using a combination of behavioral testing, molecular biology experiments, transcriptomic analysis, and non-targeted metabolomics. In individuals with SCZ, CCL11 and IL-13 levels were notably higher than in controls. In vitro, CCL11 exposure caused mitochondrial dysfunction and increased reactive oxygen species in hippocampal neurons. In vivo, CCL11-treated mice showed cognitive deficits, mitochondrial fission, and neuroinflammation in the hippocampus. Comprehensive integration of transcriptomic and metabolomic data revealed that CCL11 significantly disrupted the Glucokinase/Glucose-6-phosphate metabolism pathway, coinciding with elevated metabolites indicative of oxidative damage. Finally, downregulation of the CCR3 receptor in the hippocampus mitigated CCL11-induced oxidative stress, mitochondrial dysfunction, and cognitive impairment. CCL11 causes cytotoxicity in neurons by increasing oxidative stress and mitochondrial dysfunction. In a mouse model, knockout of the CCR3 receptor alleviates CCL11-induced cognitive impairment, mitochondrial dysfunction, and oxidative stress.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144730102","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}

引用次数: 0

Neutrophils Induce P-Selectin Shedding from Activated Platelets Via Neutrophil Elastase. 中性粒细胞通过中性弹性酶诱导p -选择素从活化血小板脱落。

IF 5 2区医学

Inflammation Pub Date : 2025-07-28 DOI: 10.1007/s10753-025-02350-0

Yingting Huang, Liqin Ling, Shanshan He, Chaonan Liu, Xunbei Huang, Shuang Wang, Zhiyu Yu, Jing Zhou

{"title":"Neutrophils Induce P-Selectin Shedding from Activated Platelets Via Neutrophil Elastase.","authors":"Yingting Huang, Liqin Ling, Shanshan He, Chaonan Liu, Xunbei Huang, Shuang Wang, Zhiyu Yu, Jing Zhou","doi":"10.1007/s10753-025-02350-0","DOIUrl":"https://doi.org/10.1007/s10753-025-02350-0","url":null,"abstract":"It is suggested that neutrophil adhesion to P-selectin (P-sel) on activated platelet can induce P-sel shedding, however, the underlying mechanism remains unclear. This study is to investigate the role of neutrophil in platelet P-sel shedding. Platelets were activated by thrombin, collagen or thrombin receptor agonist peptide (TRAP). Activated platelets were co-cultured with whole blood, peripheral blood mononuclear cells or neutrophils, in the presence or absence of lipopolysaccharide, Pam3CSK4, myeloperoxidase inhibitors, neutrophil elastase (NE) inhibitors, or Latrunculin B (LatB) (inhibiting neutrophil extracellular traps (NETs) formation but not reducing protease release). Samples were collected at 0, 1, 2, and 4 hours. P-sel expression on platelets, soluble P-sel (sP-sel), and soluble NE were assessed. P-sel shedding only occurred on platelets activated by thrombin in the presence of neutrophils (P-sel-positive platelets, 70.0%→11.1%; P-sel intensity fold decrease, 0→0.61; sP-sel fold increase, 0→6.94). This shedding was partially reversed by NE inhibitors and LatB (sP-sel fold increase: 0→3.62; 0→5.18), but accelerated by MPO inhibitors (sP-sel fold increase: 0→17.59). Soluble NE was lower in co-culture of thrombin-activated platelets and neutrophils (110.78→132.75 ng/mL), compared to co-culture of thrombin-activated platelets and LatB-treated neutrophils (144.42→153.33 ng/mL), or compared to co-culture of collagen (or TRAP)-activated platelets and neutrophils (220.39→388.04 ng/mL; 287.47→385.16 ng/mL). Lipopolysaccharide and Pam3CSK4 did not change neutrophil-induced P-sel shedding. Platelet-neutrophil interaction might be mutual. Thrombin-activated platelet promotes neutrophil activation to form NETs; and in turn, neutrophil induces platelet P-sel shedding via concentrated NE in NETs, resulting in irreversible functional downregulation of platelet P-sel-mediated interactions.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144730101","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}

引用次数: 0

Correction: Calcified Cartilage Zone Remodeling Induced by IL-1β Derived from Necrotic Subchondral Bone Initiates Cartilage Degeneration in Patients with Glucocorticoids-induced Osteonecrosis of the Femoral Head. 更正：糖皮质激素诱导的股骨头骨坏死患者由坏死软骨下骨来源的IL-1β诱导的钙化软骨区重塑引发软骨退行性变。

IF 5 2区医学

Inflammation Pub Date : 2025-07-26 DOI: 10.1007/s10753-025-02352-y

Pengbo Wang, Limei Shen, Ruitong Yang, Xu Wang, Xiangyu Wang, Yingkang Zhu, Ruiyu Liu

引用次数: 0

Stimulator of Interferon Genes Regulates Ferroptosis and Airway Inflammation via acyl-CoA Synthetase Long-Chain Family Member 4 in Asthmatic Mice. 干扰素基因刺激因子通过酰基辅酶a合成酶长链家族成员4调控哮喘小鼠铁下垂和气道炎症。

IF 4.5 2区医学

Inflammation Pub Date : 2025-07-24 DOI: 10.1007/s10753-025-02338-w

Shaotian Chen, Xinyan Jiang, Xiang Li, Tianyue Wang, Nan Yang

{"title":"Stimulator of Interferon Genes Regulates Ferroptosis and Airway Inflammation via acyl-CoA Synthetase Long-Chain Family Member 4 in Asthmatic Mice.","authors":"Shaotian Chen, Xinyan Jiang, Xiang Li, Tianyue Wang, Nan Yang","doi":"10.1007/s10753-025-02338-w","DOIUrl":"https://doi.org/10.1007/s10753-025-02338-w","url":null,"abstract":"Ferroptosis is closely associated with the various pathological manifestations of asthma. This study aimed to explore the role of the stimulator of interferon genes (STING) in modulating airway inflammation in asthma, with a particular focus on regulating ferroptosis in airway epithelial cells. Using an ovalbumin (OVA)-sensitized mouse model of asthma, the OVA group exhibited significant inflammatory cell infiltration in the airways, increased mucus secretion, and elevated levels of inflammatory cytokines compared with those noted in the normal group. Additionally, the ferroptosis-related protein acyl-CoA synthetase long-chain family member 4 (ACSL4) was upregulated, whereas glutathione peroxidase 4 (GPX4) was downregulated, accompanied by elevated malondialdehyde (MDA) levels and reduced superoxide dismutase (SOD) activity. Furthermore, both messenger ribonucleic acid and protein levels of STING were significantly increased in the lungs of OVA-sensitized mice, with predominant expression in airway epithelial cells. After intervention with STING inhibitor C-176, the OVA + C-176 group demonstrated reduced inflammatory cell infiltration and mucus hypersecretion in the airways, along with decreased serum levels of IgE and Th2-associated cytokines (IL-4 and IL-13), but increased levels of the Th1 cytokine IFN-γ. Moreover, ACSL4 protein and MDA levels were significantly decreased, whereas SOD activity was significantly restored following C-176 intervention. Double immunofluorescence staining revealed the colocalization of STING and ACSL4, with their expression levels significantly reduced following C-176 treatment. Co-immunoprecipitation confirms the interaction between STING and ACSL4. Collectively, these findings indicate that STING regulates airway inflammation in asthma by modulating ferroptosis and lipid peroxidation, highlighting STING as a potential therapeutic target for asthma.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144698361","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}

引用次数: 0

The Kynurenine Pathway in Psoriasis: Mechanisms and Therapeutic Opportunities. 牛皮癣的犬尿氨酸途径：机制和治疗机会。

IF 4.5 2区医学

Inflammation Pub Date : 2025-07-21 DOI: 10.1007/s10753-025-02339-9

Shan Huang, Yanping Bai, Xingwu Duan

{"title":"The Kynurenine Pathway in Psoriasis: Mechanisms and Therapeutic Opportunities.","authors":"Shan Huang, Yanping Bai, Xingwu Duan","doi":"10.1007/s10753-025-02339-9","DOIUrl":"https://doi.org/10.1007/s10753-025-02339-9","url":null,"abstract":"Psoriasis is a chronic inflammatory disease driven by genetic and environmental factors, with pathogenesis closely linked to metabolic reprogramming and immune microenvironment dysregulation. The kynurenine pathway (KP), as the principal route of tryptophan catabolism, plays a pivotal role in regulating immune tolerance, oxidative stress, and neuroinflammation, thereby serving as a \"metabolic bridge\" that links cutaneous lesions to systemic comorbidities in psoriasis. This review systematically examines the pathological mechanisms of KP in psoriasis. Imbalances in the activities of indoleamine 2,3-dioxygenase (IDO) and kynureninase (KYNU) in patients with psoriasis lead to a pro-inflammatory shift in KP. Moreover, downstream KP metabolites mediate oxidative damage, endothelial dysfunction, and depletion of serotonin, which are closely associated with the increased risk of cardiovascular disease and depressive disorders commonly observed in psoriasis. Although therapeutic strategies targeting the KP, such as IDO overexpression and KYNU inhibition, have demonstrated promising potential, the complexity of the metabolic network and tissue-specific effects limit the clinical application of single-target therapies. Future studies should integrate multi-omics data to elucidate the dynamic regulatory network of the KP, develop multi-targeted modulators, and explore new paradigms for coordinated management of cutaneous and systemic comorbidities, thereby providing a solid theoretical foundation for precision treatment of psoriasis.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674686","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}

引用次数: 0

HAPLN1 Exhibits Dual Effects: Facilitating Extracellular Matrix Restoration while Enhancing Inflammatory Mediator Production in Arthritic Chondrocytes. HAPLN1表现出双重作用：促进细胞外基质修复，同时增强关节炎软骨细胞中炎症介质的产生。

IF 4.5 2区医学

Inflammation Pub Date : 2025-07-19 DOI: 10.1007/s10753-025-02342-0

Yunting Chen, Chenggen Luo, Kun Huang, Xiaoli Pan, Yulei Ao, Shidan Tian, Mang He, Anmao Li, Yanjuan Chen, Mei Tian, Yong Chen

{"title":"HAPLN1 Exhibits Dual Effects: Facilitating Extracellular Matrix Restoration while Enhancing Inflammatory Mediator Production in Arthritic Chondrocytes.","authors":"Yunting Chen, Chenggen Luo, Kun Huang, Xiaoli Pan, Yulei Ao, Shidan Tian, Mang He, Anmao Li, Yanjuan Chen, Mei Tian, Yong Chen","doi":"10.1007/s10753-025-02342-0","DOIUrl":"https://doi.org/10.1007/s10753-025-02342-0","url":null,"abstract":"Hyaluronan and proteoglycan link protein 1 (HAPLN1) secreted by fibroblast-like synoviocytes (FLSs) plays a critical role in the pathological process of inflammatory arthritis. This study aimed to investigate the impact and underlying mechanisms of HAPLN1 in an inflamed chondrocyte model. IL-1β-treated SW1353 chondrocytes were exposed to recombinant HAPLN1 (rHAPLN1). A transwell coculture system was used to assess interactions between the chondrocytes and FLSs transfected with the HAPLN1 overexpression plasmid. Cell viability and proliferation were evaluated using cell counting kit-8 (CCK-8) assay and 5-ethynyl-2'-deoxyuridine (EdU) assay. RNA sequencing and bioinformatic analyses, including the identification of differentially expressed genes (DEGs), gene functional enrichment and protein-protein interaction analyses were conducted to explore the potential mechanisms. Our fundings revealed that HAPLN also increased the levels of inflammatory mediators (TNF-α, IL-6, MMP1, MMP3, MMP9, and ADAMTS-5) in the inflamed chondrocytes, suggesting its pro-inflammatory effect. However, HAPLN1 enhanced cell viability, and the expression of Collagen II and TGF-β, the restoration effect of extracellular matrix (ECM). Bioinformatics analysis suggested the upregulated DEGs were enriched in the inflammatory processes, and the pathways related to ECM, TNF and IL-6 were activated in inflamed chondrocytes following rHAPLN1 exposure. Additionally, the protein-protein interaction networks indicated that HAPLN1 interacts with the molecules related to ECM, inflammation, and PI3K/AKT/mTOR pathway. Western blot assay further verified that the phosphorylation of PI3K, AKT, and mTOR was elevated in the rHAPLN1-treated chondrocytes. Our findings highlight the dual effects of HAPLN1 on the arthritic chondrocytes, which may be associated with the activation of the PI3K/AKT/mTOR pathway.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667542","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}

引用次数: 0

From Homeostasis To Inflammation To Autoimmunity: The Potential Impact of CRP. 从体内平衡到炎症再到自身免疫：CRP的潜在影响。

IF 4.5 2区医学

Inflammation Pub Date : 2025-07-18 DOI: 10.1007/s10753-025-02303-7

Mustafa Ahmed, Ping Yuan, Jia-Geng Lei, Zhao-Ming Tang, Ze-Rui Yang, Lawrence A Potempa, Hui-Ying Wang, Hai-Yun Li

{"title":"From Homeostasis To Inflammation To Autoimmunity: The Potential Impact of CRP.","authors":"Mustafa Ahmed, Ping Yuan, Jia-Geng Lei, Zhao-Ming Tang, Ze-Rui Yang, Lawrence A Potempa, Hui-Ying Wang, Hai-Yun Li","doi":"10.1007/s10753-025-02303-7","DOIUrl":"https://doi.org/10.1007/s10753-025-02303-7","url":null,"abstract":"C-reactive protein (CRP) is a highly conserved pentraxin, synthesized primarily in the liver, and is widely recognized as a highly sensitive biomarker for inflammation and tissue damage. While considerable research has focused on elucidating the structural and functional aspects of CRP, along with its utility as a biomarker reflecting disease severity and activity, the understanding of distinctive CRP structural isoforms is evolving. Its role is not only as a biomarker but also as a regulator of both physiologic and pathophysiologic processes of inflammation and autoimmune pathology. In this review, we systematically reviewed the role of CRP and its monomeric form, mCRP, in autoimmune disorders like inflammatory bowel disease (IBD), rheumatoid arthritis (RA), systemic sclerosis (SSc), and psoriasis. It investigates their impact on immune dysregulation, tissue damage, and disease progression. The review also discusses studies suggesting CRP and mCRP as potential therapeutic targets to manage inflammation and maintain immune balance in autoimmune diseases and provide insights for future research and therapeutic approaches in autoimmune disease management.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659123","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}

引用次数: 0

miR-182-Mediated Dysregulation of Histidine Metabolism Compromises T Cell Immunity in Sepsis. mir -182介导的组氨酸代谢失调损害败血症中的T细胞免疫。

IF 4.5 2区医学

Inflammation Pub Date : 2025-07-17 DOI: 10.1007/s10753-025-02333-1

Yaolu Zhang, Jie Lian, Lujia Zhu, Yamei Wei, Kaikai Wang, Zhongqiu Lu, Longwang Chen

{"title":"miR-182-Mediated Dysregulation of Histidine Metabolism Compromises T Cell Immunity in Sepsis.","authors":"Yaolu Zhang, Jie Lian, Lujia Zhu, Yamei Wei, Kaikai Wang, Zhongqiu Lu, Longwang Chen","doi":"10.1007/s10753-025-02333-1","DOIUrl":"https://doi.org/10.1007/s10753-025-02333-1","url":null,"abstract":"MicroRNA-182 (miR-182) exhibits immunomodulatory effects in regulating inflammatory responses to bacterial infection. However, the involvement of miR-182 in regulating T-cell immune function and differentiation in sepsis remains unknown. This study investigated the role of miR-182 in regulating T cell immune function and its mechanism in sepsis-induced immunosuppression. Using the cecum ligation and puncture model to mimic experimental sepsis, we found a significant reduction in splenic lymphocyte numbers and dysregulated T cell differentiation in septic mice. miR-182 expression was elevated in septic mice. Its knockout improved T cell immune function, ameliorated organ damage and improved survival rates in septic mice. Metabolomic and proteomic profiling revealed that histidine catabolism was attenuated and histidine was increased after miR-182 knockout. L-histidine supplementation alleviated T-cell immunosuppression in vivo. In addition, elevated plasma miR-182 levels were correlated with poor clinical prognosis in sepsis patients. Our findings demonstrate that miR-182 deficiency ameliorates the immunosuppression of T cells through the modulation of histidine metabolism, offering novel insights into the molecular mechanisms underlying T-cell dysfunction in sepsis.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144649315","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}

引用次数: 0