International immunopharmacology最新文献

{"title":"Astragaloside III inhibits MAPK-mediated M2 tumor-associated macrophages to suppress the progression of lung Cancer cells via Akt/mTOR signaling pathway","authors":"Yan Sun ,&nbsp;Jia-Qi Liu ,&nbsp;Wen-Jing Chen ,&nbsp;Wei-Feng Tang ,&nbsp;Yao-Long Zhou ,&nbsp;Bao-Jun Liu ,&nbsp;Ying Wei ,&nbsp;Jing-Cheng Dong","doi":"10.1016/j.intimp.2025.114546","DOIUrl":"10.1016/j.intimp.2025.114546","url":null,"abstract":"<div><div>Tumor-associated macrophages (TAMs) play a key role in facilitating a range of cancerous processes by modulating the tumor microenvironment thus being a target for cancer treatment. Astragaloside III (AS-III), a compound derived from Astragalus triterpenoid saponins, has demonstrated immunomodulatory and anticancer properties, but the underlying mechanism remains unclear. Here, we demonstrated that AS-III suppressed metastasis, angiogenesis and induced apoptosis of lung cancer <em>in vitro</em> and <em>in vivo</em> by inhibiting macrophage M2 polarization and inducing M1 phenotype transformation. This was achieved through the inhibition of the MAPK signaling pathway. Furthermore, the tumor inhibitory effects of AS-III were found to be mediated by the Akt/mTOR pathway. Overall, these results highlight the role of AS-III in modifying the TAMs in TME, offering fresh perspectives on tumor immunotherapy by means of targeting macrophage.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"154 ","pages":"Article 114546"},"PeriodicalIF":4.8,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143768735","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":"Plasma and urine metabolomics for the identification of diagnostic biomarkers for sulfur mustard-induced lung injury","authors":"Vahid Jamshidi ,&nbsp;Hasan Bagheri ,&nbsp;Nahid Safari-Alighiarloo ,&nbsp;Mahmood Salesi ,&nbsp;Sadegh Azimzadeh J. ,&nbsp;Shahram Parvin ,&nbsp;Mostafa Ghanei ,&nbsp;B. Fatemeh Nobakht M. Gh.","doi":"10.1016/j.intimp.2025.114515","DOIUrl":"10.1016/j.intimp.2025.114515","url":null,"abstract":"<div><h3>Background</h3><div>Sulfur mustard (SM) is a highly lethal chemical warfare agent that induces severe health complications in exposed individuals. Gaining insights into the metabolic changes caused by SM exposure is essential for understanding its underlying mechanisms and developing effective diagnostic and therapeutic interventions.</div></div><div><h3>Methods</h3><div>In this investigation, we utilized proton nuclear magnetic resonance (H-NMR) spectroscopy to conduct metabolomic analysis in patients diagnosed with mustard lung disease (MLD) using a non-targeted approach. Metabolite measurements were conducted on plasma and urine samples collected from a total of 54 individuals, including 20 individuals with mild MLD, 20 individuals with moderate MLD, and 14 healthy individuals. Multivariate and univariate analyses were applied to identify metabolites that distinguish between the different groups, and enrichment analysis was performed to unveil the underlying biochemical pathways involved.</div></div><div><h3>Results</h3><div>The obtained metabolic profile had the potential to differentiate moderate from healthy plasma, but not from mild patients using multivariate analysis. Sixteen metabolites from plasma were considered significantly different between the moderate and control groups (VIP &gt; 1 and <em>p</em> &lt; 0.05) that these metabolites involved in fatty acid and amino acid metabolism. Utilizing all 16 metabolites as a combined panel, we were able to distinguish between the moderate and control groups, achieving an area under the curve (AUC) of 0.854. Moreover, 6 and 8 urinary metabolites were detected between mild vs. control and moderate vs. control groups, respectively. Fourteen metabolites exhibited significant fold changes (FC) (FC &lt; 0.66 or FC &gt; 1.5; <em>p</em> &lt; 0.05). These metabolites are involved in amino acid and nicotinate metabolism.</div></div><div><h3>Conclusion</h3><div>Our study provides novel insights into the metabolic changes associated with MLD and highlights potential pathways involved in the disease progression. These findings have implications for the development of targeted diagnostic and therapeutic strategies for MLD.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"154 ","pages":"Article 114515"},"PeriodicalIF":4.8,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143768736","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":"Modulating the NLRP3 Inflammasome: Acitretin as a potential treatment for Sepsis-induced acute lung injury","authors":"Huikang Xu ,&nbsp;Haowen Xu ,&nbsp;Weifeng Li ,&nbsp;Zhiyu Liang ,&nbsp;Weiwei Luo ,&nbsp;Shiying Sheng ,&nbsp;Guang Liang ,&nbsp;Zhaocai Zhang","doi":"10.1016/j.intimp.2025.114504","DOIUrl":"10.1016/j.intimp.2025.114504","url":null,"abstract":"<div><h3>Background</h3><div>Acitretin, a well-established dermatological drug primarily used for psoriasis treatment, has been clinically used for several decades. However, its potential role in modulating inflammation in sepsis remains unexplored.</div></div><div><h3>Objective</h3><div>This study seeks to explore the impact of acitretin on sepsis-induced acute lung injury (ALI) and to elucidate the underlying mechanisms involved.</div></div><div><h3>Methods</h3><div>In a mouse model of sepsis induced by lipopolysaccharide (LPS), we assessed the effects of acitretin on ALI. Transcriptome sequencing of lung tissue was performed to identify relevant signaling pathways. <em>In vitro</em>, bone marrow-derived macrophages (BMDMs) were treated with acitretin (1 μM, 5 μM and 10 μM) to evaluate its impact on NOD-, LRR- and pyrin domain-containing protein 3(NLRP3) inflammasome activation and pyroptosis. <em>In vivo</em>, wild-type, <em>Nlrp3</em> knockout, and <em>Gsdmd</em> knockout mice were used to confirm the role of the NLRP3 inflammasome in mediating acitretin's effects.</div></div><div><h3>Results</h3><div>Acitretin significantly mitigated sepsis-induced ALI, reducing mortality in LPS-challenged mice. Transcriptome analysis revealed that acitretin suppressed the NLRP3 inflammasome pathway in lung tissue. <em>In vitro</em>, acitretin dose-dependently inhibited interleukin (IL)-1β release, caspase-1 p20 production, and GSDMD cleavage in BMDMs. Furthermore, acitretin inhibited inflammasome activation by preventing ASC oligomerization and its interaction with NLRP3. <em>In vivo</em>, acitretin reduced lung tissue inflammation, IL-1β levels in bronchoalveolar lavage fluid, and the ratio of wet to dry in wide-type mice, but these effects were abolished in <em>Nlrp3</em> and <em>Gsdmd</em> knockout mice.</div></div><div><h3>Conclusion</h3><div>Acitretin demonstrated significant anti-inflammatory properties through the suppression of the NLRP3 inflammasome, suggesting its potential as a therapeutic strategy for sepsis and related complications.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"153 ","pages":"Article 114504"},"PeriodicalIF":4.8,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143761231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dysregulated glutathione metabolism impairs natural killer cell function in patients with acute leukemia","authors":"Yue Zhao ,&nbsp;Yan Wang ,&nbsp;Tingting Liang ,&nbsp;Xian Song ,&nbsp;Yingqiao Zhu ,&nbsp;Xinru Liu ,&nbsp;Mengya Lv ,&nbsp;Changcheng Zheng ,&nbsp;Fang Ni","doi":"10.1016/j.intimp.2025.114566","DOIUrl":"10.1016/j.intimp.2025.114566","url":null,"abstract":"<div><div>Natural killer (NK) cell function is markedly impaired in patients with acute leukemia, weakening their anti-tumor immune response. However, the mechanisms underlying NK cell dysfunction are not fully understood. Here, we reveal that NK cells from patients with acute leukemia (AL-NK) exhibit significantly reduced intracellular glutathione (GSH) levels, accompanied by disrupted redox homeostasis and increased levels of mitochondrial reactive oxygen species. Flow cytometry and transcriptomic analyses indicate that dysregulated GSH metabolism leads to mitochondrial dysfunction in NK cells, thereby impairing their antileukemic cytotoxicity and proliferative capacity. Notably, supplementation with glutathione reduced ethyl ester (GSHEE)—a GSH precursor—effectively restores GSH levels in AL-NK cells, enhancing mitochondrial activity, oxidative phosphorylation, ATP production, and NK cell-mediated cytotoxicity. Moreover, GSHEE treatment activates the mTOR signaling pathway in NK cells, further promoting their function and proliferation. Overall, our study identifies dysregulated GSH metabolism as a key driver of NK cell dysfunction in acute leukemia and suggests that GSH-based interventions may provide a promising strategy to enhance NK cell-mediated immunotherapies.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"154 ","pages":"Article 114566"},"PeriodicalIF":4.8,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143759825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adiponectin receptor agonist adipoRon alleviates imiquimod-induced murine psoriasis","authors":"Geng Sun ,&nbsp;Hai-Qian Zhao ,&nbsp;Yuan-Yuan Huang ,&nbsp;Zhan-Ying Guo ,&nbsp;Lin Zhang ,&nbsp;Hao Zhu ,&nbsp;Xin-Yue Wang ,&nbsp;Hao-Nan Ye ,&nbsp;Cai-Ping Chen","doi":"10.1016/j.intimp.2025.114568","DOIUrl":"10.1016/j.intimp.2025.114568","url":null,"abstract":"<div><div>Psoriasis is a chronic inflammatory skin disease involving inflammation, immune responses and keratinocytes proliferation. It has been suggested that adiponectin/adiponectin receptor 1 (AdipoR1) signaling plays a role in regulating psoriatic skin inflammation. AdipoRon is a small molecule agonist of AdipoR1 and AdipoR2. The effect of adipoRon on psoriasis has not been elucidated. In this study, using a GEO database, we found that the expression of adiponectin was substantially decreased in skin lesions of psoriasis patients. This reduction was also validated in an imiquimod-induced psoriasis mouse model. Interestingly, we found that topical administration of adipoRon significantly ameliorated skin lesions induced by imiquimod. The critical pro-inflammatory cytokines (IL-6, IL-17A and IL-23) and the infiltration of macrophages, especially M1 macrophages were dramatically decreased while the infiltration of M2 macrophages were slightly increased in the skin lesions upon adipoRon treatment. Mechanistically, adipoRon inhibited macrophage inflammation and keratinocytes proliferation <em>via</em> activation of AMPK signaling pathway. Collectively, our study demonstrates that adipoRon displayed anti-inflammatory activity and anti-proliferation of keratinocytes, and attenuated psoriatic response. Activating AdipoR1 signaling pathway by adipoRon or others may represent a novel therapeutic approach to psoriasis.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"154 ","pages":"Article 114568"},"PeriodicalIF":4.8,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143768732","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":"Dynamic assessment of myelofibrosis progression in myeloproliferative neoplasm mouse model using a minimally invasive evaluation system","authors":"Xiaohe Gu ,&nbsp;Xuguang Song ,&nbsp;Ke Yuan ,&nbsp;Yahui Liu ,&nbsp;Yanjie Li ,&nbsp;Jianlin Qiao ,&nbsp;Wen Ju ,&nbsp;Shengnan Yuan ,&nbsp;Yue Li ,&nbsp;Weiwei Wang ,&nbsp;Lingyu Zeng","doi":"10.1016/j.intimp.2025.114567","DOIUrl":"10.1016/j.intimp.2025.114567","url":null,"abstract":"<div><div>Myelofibrosis (MF) is the most common complication of myeloproliferative neoplasms (MPNs)，which is markedly correlated with a dismal prognosis. Murine model such as the thrombopoietin receptor (MPL)W515L-mutant MPN mouse model functions as a crucial vehicle in disease research, is widely used in basic and applied research on MPNs and MF.However, the lack of methods for dynamic observation of MF progression hinders mechanistic studies and drug development for MF.</div><div>Here we develop a sensitive, stable and minimally invasive MPN evaluation system to assess the evolution of myelofibrosis in murine model.Key peripheral blood parameters (WBC, RBC, HGB, HCT, PLT, and tumor cell proportion) from MPN mice were analyzed using PCA to reduce dimensionality and generate a comprehensive evaluation score (Y). Based on peripheral blood smear observations and predefined score cut-off values (0.59 and − 0.44), MPN was classified into mild, moderate, and severe stages. Validation conducted across diverse experimental settings yielded outcomes that were in alignment with the pathological grading of myelofibrosis. This system facilitated the dynamic monitoring of MF progression in applied research on pigment epithelium-derived factor treatment for MPN and basic studies on the role of NLRP inflammasomes in the bone marrow microenvironment.</div><div>We believed that this minimally invasive evaluation system for grading MF severity in MPN mouse model will provide a potential tool for MPN pathogenesis research and targeted therapy development.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"154 ","pages":"Article 114567"},"PeriodicalIF":4.8,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143748164","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":"Programmed cell death 1 inhibitor combined with chemotherapy compared to chemotherapy alone as first-line treatment in advanced gastric cancer patients: A real-world study","authors":"Yunqi Hua ,&nbsp;Yuqian Gao ,&nbsp;Shuang Luo ,&nbsp;Ge Song ,&nbsp;Xiaoling Tian ,&nbsp;Chenlin Wang ,&nbsp;Shuang Lv ,&nbsp;Xinyi Zhang ,&nbsp;Guo Shao","doi":"10.1016/j.intimp.2025.114487","DOIUrl":"10.1016/j.intimp.2025.114487","url":null,"abstract":"<div><h3>Objective</h3><div>Previous trials have revealed better treatment efficacy of programmed cell death 1 (PD-1) inhibitors combined with chemotherapy as first-line treatments than chemotherapy alone in advanced gastric cancer (GC) patients, but real-world evidence is still lacking. Hence, this real-world study aimed to investigate the efficacy and safety of PD-1 inhibitors plus chemotherapy as first-line treatments compared with chemotherapy alone in advanced GC patients.</div></div><div><h3>Methods</h3><div>In total, 102 advanced GC patients were allocated into a combination group (receiving chemotherapy combined with a PD-1 inhibitor as a first-line treatment) (<em>n</em> = 48) or a chemotherapy group (receiving chemotherapy only as a first-line treatment) (<em>n</em> = 54) according to their actual treatment regimens.</div></div><div><h3>Results</h3><div>The objective response rate (ORR) was greater in the combination group than in the chemotherapy group (25.0 % versus 9.3 %, <em>P</em> = 0.033), whereas the disease control rate (DCR) was not different between the groups (83.3 % versus 66.7 %, <em>P</em> = 0.054). Progression-free survival (PFS) was prolonged in the combination group than in the chemotherapy group (<em>P</em> = 0.018). The median (95 % confidence interval) PFS was 19.7 (12.2–27.2) months in the combination group and 16.5 (7.3–25.7) months in the chemotherapy group. Multivariate logistic regression analyses revealed that PD-1 inhibitors combined with chemotherapy were independently associated with an increased ORR (odds ratio: 4.180, <em>P</em> = 0.024), increased DCR (odds ratio: 2.928, <em>P</em> = 0.049), and prolonged PFS (hazard ratio: 0.388, <em>P</em> = 0.030). No difference was found in total or each specific grade III-IV adverse reaction between the groups (all <em>P</em> &gt; 0.05).</div></div><div><h3>Conclusion</h3><div>Treatment with a PD-1 inhibitor plus chemotherapy as a first-line treatment shows better treatment efficacy with similar safety to that of chemotherapy alone in advanced GC patients.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"154 ","pages":"Article 114487"},"PeriodicalIF":4.8,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143759824","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":"Human antigen R -mediated autophagy-related gene 3 methylation enhances autophagy-driven ferroptosis in Crohn's disease colitis","authors":"Zhipeng Li,&nbsp;Yunxiang Chang,&nbsp;Di He,&nbsp;Kai Dong,&nbsp;Hongzhen Zhang,&nbsp;Shikai Wang","doi":"10.1016/j.intimp.2025.114565","DOIUrl":"10.1016/j.intimp.2025.114565","url":null,"abstract":"<div><h3>Background and Aims</h3><div>Crohn's disease (CD) is a chronic inflammatory disorder that can affect any part of the gastrointestinal tract, with the exact etiology remaining unclear. Recent studies have implicated the role of human antigen R (HuR) in the pathogenesis of various inflammatory diseases, including CD. However, the role of HuR in the modulation of CD remains underexplored. Therefore, this study aimed to investigate the mechanistic involvement of HuR in CD.</div></div><div><h3>Methods</h3><div>We established colitis models using human intestinal epithelial cells and lipopolysaccharide and dextran sulfate sodium-induced mice. Additionally, by knocking out HuR in both cell and animal models, we validated the role of HuR in autophagy and ferroptosis. The role of HuR in regulating ferroptosis accompanied by autophagy activation in CD was detected using ELISA, flow cytometry, immunofluorescence, transmission electron microscopy, Western blot, and RT-qPCR. The demethylation level of ATG3 and the stability of ATG3 mRNA regulated by HuR were detected using immunofluorescence, RIP, and MeRIP-qPCR. The effect of HuR on DSS-induced colitis was evaluated using DAI score, H&amp;E staining, TUNEL staining, and immunohistochemistry.</div></div><div><h3>Results</h3><div>The results show that HuR expression is significantly increased in CD colonic inflammation. Compared with the control group, the model group mice exhibited decreased levels of lipid peroxidation markers glutathione and superoxide dismutase, elevated malondialdehyde and reactive oxygen species levels, and reduced expression of iron-related proteins glutathione peroxidase 4, ferritin heavy chain protein 1, and solute carrier family 7 member 11. Additionally, the expression of autophagy-related proteins microtubule-associated protein 1 A/1B-light chain 3, beclin-1, and autophagy related 3 (ATG3) was upregulated, while p62 expression was downregulated. In both in vitro and in vivo models, HuR knockout reversed these changes induced by lipopolysaccharide and dextran sulfate sodium, concomitant with improved tissue pathology. Mechanistically, HuR enhances autophagy-mediated ferroptosis in CD colonic inflammation by regulating ATG3 methylation and mRNA stability.</div></div><div><h3>Conclusion</h3><div>HuR accelerates colonic inflammation in CD by regulating ATG3 methylation, which enhances autophagy-mediated ferroptosis. Knockout of HuR alleviates Crohn's colitis. This finding provides a potential therapeutic target for the treatment of CD.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"154 ","pages":"Article 114565"},"PeriodicalIF":4.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143739873","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":"Efficacy and safety of telitacicept in patients with class III–V lupus nephritis: A real-world retrospective cohort study","authors":"Lin Chen ,&nbsp;Yuwen Teng ,&nbsp;Qiuling Ma ,&nbsp;Wenqing Liu ,&nbsp;Wenbo Dong ,&nbsp;Ruiqiang Wang","doi":"10.1016/j.intimp.2025.114596","DOIUrl":"10.1016/j.intimp.2025.114596","url":null,"abstract":"<div><h3>Objectives</h3><div>This retrospective cohort study evaluated the efficacy and safety of telitacicept combined with standard therapy in class III–V lupus nephritis (LN).</div></div><div><h3>Methods</h3><div>We enrolled 146 patients with lupus nephritis confirmed by renal biopsy. Among them, 73 patients received treatment with telitacicept in combination with the standard therapy regimen, while the remainder were treated with the standard therapy alone. This analysis included class III/IV ± V or class V LN. Efficacy endpoints included cumulative complete renal response (CRR, 24hUTP &lt; 0.5 g with stable renal function) and partial renal response (PRR, 50 % reduction in 24hUTP from baseline) at 6 months, 1 year, and the end of follow-up. Multivariate regression was used to assess baseline predictors of CRR. Safety was also evaluated.</div></div><div><h3>Results</h3><div>Compared with the control group, telitacicept showed remarkable efficacy in improving disease activity indicators such as serum albumin (ALB), complement levels, and 24-h urinary total protein (24hUTP), with a significant reduction in antibody positivity rates and immunoglobulin levels, alongside an improvement in anemia. By 6 months, the CRR rate in the telitacicept group reached 64.4 % (64.4 % vs 45.2 %, <em>P</em> = 0.020). At 1 year, the cumulative CRR was significantly higher in the telitacicept group compared to the control group (80.8 % vs 61.6 %; <em>P</em> = 0.010). During follow-up, the time to achieve CRR was significantly earlier in the telitacicept group (median 4.0 months, 95 %CI, 2.71–5.29) than in the control group (median 9.0 months, 95 %CI, 5.25–12.75) (LogRank <em>P</em> = 0.006). Moreover, subgroup analyses indicated better efficacy of telitacicept in patients with positive dsDNA antibodies (OR, 1.70, 95 %CI, 1.20–2.40, P for interaction = 0.031). Telitacicept dose reduction did not increase disease activity. Multivariate analysis showed that the use of telitacicept was a favorable factor for achieving CRR, and other predictors included BMI, eGFR, and 24hUTP. Compared with the standard treatment group, the risk of adverse renal outcome events in the telitacicept group was reduced by 53 %. The incidence of adverse events was similar between the two groups.</div></div><div><h3>Conclusions</h3><div>This real-event study confirmed that the addition of telitacicept to standard therapy significantly boosted clinical remission rates and improved prognosis in patients with LN. It was also found that telitacicept may be more likely to achieve CRR in dsDNA antibody-positive patients. At baseline, the use of telitacicept, lower BMI and 24hUTP levels, and higher eGFR levels were associated with a greater likelihood of achieving CRR. In addition, for patients who achieve CRR and SLEDAI score ≤ 6, we advocate dose reduction of telitacicept after 6 months of treatment.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"154 ","pages":"Article 114596"},"PeriodicalIF":4.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143739874","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":"IsoalloLCA-intervened regulatory T cell exosomes alleviate inflammatory bowel disease by inhibiting NF-κB-associated inflammation in intestinal epithelial cells","authors":"Simei Yue ,&nbsp;Lingjiao Gong ,&nbsp;Yulin Tan ,&nbsp;Xiaodan Zhang ,&nbsp;Fei Liao","doi":"10.1016/j.intimp.2025.114501","DOIUrl":"10.1016/j.intimp.2025.114501","url":null,"abstract":"<div><div>Regulatory T cells (Tregs) are the principal immune cells that exert anti-inflammatory effects within the organism. Their exosomes exhibit therapeutic efficacy across a broad spectrum of diseases owing to their high stability, low immunogenicity, and substantial penetration capacity. Recent research have indicated that isoallolithocholic acid (isoalloLCA), a metabolite associated with bile acid metabolism, may enhance Treg activity by upregulating forkhead box protein3 (Foxp3) expression. Hence, metabolite-based strategies for reinforcing Tregs may offer novel intervention options for treating related diseases. In this study, tumor necrosis factor (TNF)-α and dextran sulfate sodium (DSS) were employed to establish cellular and animal models of inflammatory bowel disease (IBD), further evaluating the therapeutic efficacy of isoalloLCA-intervened regulatory T cell exosomes (isoalloLCA-Exo) within this model. Our findings demonstrated that isoalloLCA-Exo effectively inhibit colitis progression in a murine model, as indicated by reduced inflammation, decreased apoptosis of intestinal epithelial cells, and improved intestinal barrier function. Furthermore, in vitro analyses elucidated the molecular mechanisms underlying the anti-inflammatory effects of isoalloLCA-Exo, revealing that the intervention effectively reversed TNF-α-induced inflammation and apoptosis in intestinal epithelial cells by modulating the NF-κB pathway. In conclusion, isoalloLCA-Exo can decelerate inflammatory bowel disease progression and suppress inflammatory response in intestinal epithelial cells by inhibiting NF-κB pathway. Notably, isoalloLCA-Exo exhibit superior efficacy to the traditional drug mesalazine and conventional treg exosome(NC-Exo). These findings have significant implications for optimizing Treg-derived exosome-based therapies for inflammation-related diseases.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"154 ","pages":"Article 114501"},"PeriodicalIF":4.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143748163","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}