ImmunoTargets and Therapy最新文献

{"title":"Prognostic Significance of Circulating Immune Subset Counts in Nasopharyngeal Carcinoma.","authors":"Honghui Xie, Lin Zhang, Lizhi Chen, Wenchao Zhou, Lijuan Zhang, Yong Su, Bocheng Li, Peng Ding, Yun Xiao, Tianzhu Lu, Xiaochang Gong, Jingao Li","doi":"10.2147/ITT.S516853","DOIUrl":"10.2147/ITT.S516853","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to assess the prognostic value of circulating immune cells in newly diagnosed, non-metastatic nasopharyngeal carcinoma (NPC) and to develop a nomogram combining immune cell counts with clinical characteristics.</p><p><strong>Methods: </strong>In this retrospective study, patients with non-metastatic NPC treated between January 2015 and December 2018 were included. Circulating immune cell subtypes were measured using cellular immunochip technology. Survival outcomes were assessed using Kaplan-Meier analysis, and independent prognostic factors were identified through multivariate analysis (MVA). A prognostic nomogram was constructed and evaluated using Harrell's concordance index (C-index).</p><p><strong>Results: </strong>A total of 459 patients were included, with a median follow-up of 62 months. Optimal cutoff values for CD4+ T cells (420 cells/μL), CD8+ T cells (430 cells/μL), CD3+ T cells (1100 cells/μL), and CD4/CD8 ratio (1.00) were determined using X-tile. Higher levels of CD4+ T cells (78.6% vs 64.2%, p < 0.001), CD8+ T cells (77.5% vs 71.4%, p = 0.113), CD3+ T cells (83.1% vs 70.0%, p = 0.003), and CD4/CD8 ratio (77.6% vs 60.0%, p = 0.001) were associated with better 5-year progression-free survival. MVA confirmed high CD4/CD8 ratio and CD3+ T cell count as independent prognostic factors. The nomogram combining CD3+ T cells, CD4/CD8 ratio, and N classification showed superior prognostic accuracy compared with the clinical model alone (C-index: 0.686 vs 0.648, p < 0.001).</p><p><strong>Conclusion: </strong>Circulating immune cells, particularly CD3+ T cells and CD4/CD8 ratio, are significant prognostic indicators in NPC. The proposed nomogram may help predict disease progression and support individualized treatment planning.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"577-587"},"PeriodicalIF":6.2,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12182246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144369231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Regulatory Network of Transcription Factors in Macrophage Polarization.","authors":"Jie Liu, Mengran Wang, Yong Zhao","doi":"10.2147/ITT.S494550","DOIUrl":"10.2147/ITT.S494550","url":null,"abstract":"<p><p>Macrophage polarization, a dynamic process crucial for immune responses and tissue homeostasis, is tightly regulated by transcription factors. Understanding the transcriptional regulation of macrophage polarization holds significant therapeutic implications for various diseases, including cancer, autoimmune disorders, and metabolic syndromes. Studies have shown that transcription factors, including signal transducer and activator of transcription (STAT), nuclear transcription factor-κB (NF-κB), peroxisome proliferator-activated receptors (PPARs), interferon regulatory factors (IRFs), BTB and CNC homology (BACH), CCAAT-enhancer binding proteins (C/EBPs), kruppel-like factors (KLFs), Cellular Myc (c-Myc), the SNAIL family, v-Maf Musculoaponeurotic Fibrosarcoma Oncogene Homolog (Maf), and hypoxia-inducible factor alpha (HIFα), are highly involved in shaping macrophage polarization. Targeting transcription factors involved in macrophage polarization may provide promising avenues for immunomodulatory therapies aimed at restoring immune homeostasis and combating pathological conditions characterized by dysregulated macrophage activation. Here, we review the intricate transcriptional networks that govern macrophage polarization, highlighting the pivotal role of transcription factors in orchestrating these processes.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"555-575"},"PeriodicalIF":6.2,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12151090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144267484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"JAK-STAT Signaling in Autoimmunity and Cancer.","authors":"Sana Parveen, Mariyam Fatma, Snober Shabnam Mir, Said Dermime, Shahab Uddin","doi":"10.2147/ITT.S485670","DOIUrl":"https://doi.org/10.2147/ITT.S485670","url":null,"abstract":"<p><p>The JAK-STAT pathway is an essential cell survival signaling that regulates gene expressions related to inflammation, immunity and cancer. Cytokine receptors, signal transducer and activator of transcription (STAT) proteins, and Janus kinases (JAKs) are the critical component of this signaling cascade. When JAKs are stimulated by cytokines, STAT phosphorylation, dimerization, and nuclear translocation occur, which eventually impacts gene transcription. Dysregulation of JAK-STAT signaling is linked with various autoimmune diseases, including rheumatoid arthritis, psoriasis, and inflammatory bowel disease. This pathway is constitutively activated in human malignancies and leads to tumor cell survival, proliferation, and immune evasion. Oncogenic mutations in the JAK and STAT genes have been found in solid tumors, leukemia, and lymphoma. Targeting the JAK-STAT pathway is a viable and promising therapeutic strategy for the treatment of autoimmune diseases and cancers.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"523-554"},"PeriodicalIF":6.2,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12080488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How to Choose Treatment Regimens for Idiopathic Membranous Nephropathy Patients with PLA2R-Negative: A Single-Center Retrospective Cohort Study.","authors":"Zijian Zhou, Yijing Zou, Ben Ke, Wen Shen","doi":"10.2147/ITT.S512451","DOIUrl":"https://doi.org/10.2147/ITT.S512451","url":null,"abstract":"<p><strong>Background: </strong>Cyclophosphamide, tacrolimus, and rituximab (RTX) are first-line treatments for idiopathic membranous nephropathy (IMN), regardless of PLA2R status. While the efficacy of RTX in IMN patients with PLA2R-positive has been well-documented, its effectiveness in IMN patients with PLA2R-negative remains understudied. This study aimed to evaluate the efficacy and adverse events of these three treatment regimens in IMN patients with PLA2R-negative.</p><p><strong>Methods: </strong>This study included 46 PLA2R-negative IMN patients confirmed by renal biopsy and immunofluorescence from the Department of Nephrology, the Second Affiliated Hospital of Nanchang University between September 2021 and October 2023. We compared clinical remission rates, and side effects at 3, 6, and 12 months follow-up in 14 patients who received prednisolone combined with cyclophosphamide (cyclophosphamide group), in 11 patients who treated with prednisolone combined with tacrolimus (tacrolimus group), and 21 patients who treated with rituximab (RTX group).</p><p><strong>Results: </strong>Baseline characteristics were similar among the three groups. At the 12-month follow-up, the complete response rate was significantly higher in the cyclophosphamide and tacrolimus groups compared to the RTX group (<i>p</i> = 0.029). However, there were no significant differences in cumulative complete remission rates or cumulative composite remission rates among the three groups during the follow-up period (<i>p</i> = 0.192, <i>p</i> = 0.212). Severe adverse events occurred in all groups, but the differences were not statistically significant (<i>p</i> > 0.05).</p><p><strong>Conclusion: </strong>Cyclophosphamide and tacrolimus appear to offer long-term benefits for PLA2R-negative IMN patients, with tacrolimus demonstrating superior efficacy among the treatment options evaluated. These insights offer important guidance for clinical decision-making in the management of PLA2R-negative IMN. However, further large-scale, multicenter studies with long-term follow-up are necessary to confirm these findings.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"515-522"},"PeriodicalIF":6.2,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12065463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144017143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell-Based Therapeutic Strategies for Autoimmune Diseases.","authors":"Francisco B Quero, Tays Troncoso-Bravo, Mónica A Farías, Alexis M Kalergis","doi":"10.2147/ITT.S513629","DOIUrl":"https://doi.org/10.2147/ITT.S513629","url":null,"abstract":"<p><p>Currently, the management of autoimmune disorders still being a challenge in terms of safety, efficiency, and specificity. Cell-based therapeutic strategies have emerged as a novel approach for autoimmune disease treatment, employing different cell therapy platforms, including tolerogenic dendritic cells, regulatory T cells, conventional and regulatory chimeric antigen receptor-T cells, mesenchymal and hematopoietic stem cells, each with their biological features. Here, we discuss the different cell therapy platforms, their immunological mechanisms of action, their therapeutic potential and benefits in autoimmune diseases, and challenges related to their production, scaling up, risks, and patient safety.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"501-514"},"PeriodicalIF":6.2,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12047289/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144051113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-GAD65 Antibodies Related Refractory Epilepsy Successfully Treated with Tocilizumab: A Case Report and Systematic Literature Review.","authors":"Shimeng Chen, Miriam Kessi, Jielu Tan, Fang He, Ciliu Zhang, Fei Yin, Lifen Yang, Jing Peng","doi":"10.2147/ITT.S520026","DOIUrl":"https://doi.org/10.2147/ITT.S520026","url":null,"abstract":"<p><strong>Background: </strong>Although anti-GAD65 related epilepsy is rare, it needs more attention because it is refractory to the conventional therapies, has poor outcome and high relapse rate. In this study, we intended to report the efficacy of tocilizumab in the treatment of anti-GAD65 antibodies related refractory epilepsy based on our center's experience and literature review.</p><p><strong>Methods: </strong>The clinical data of the patients managed with tocilizumab at Xiangya Hospital and those from the literature was collected and analysed.</p><p><strong>Results: </strong>A female child presented at our center with neuropsychiatric symptoms and generalized tonic-clonic seizures (including status epilepticus) at the age of 3 years. She had positive anti-GAD65 autoantibodies. Her initial electroencephalograph showed multi-focal epileptic discharges and an early brain magnetic resonance imaging demonstrated increased intensity in the bilateral hippocampi and right insular cortex. She received several anti-seizures medications (ASMs) and immunotherapies without significant improvement; however, she experienced significant clinical, electrographic and radiological improvement after receiving four cycles of the tocilizumab. Literature review unveiled two more female cases. The mean age of seizure onset for three cases was 7.72 years, and they presented with refractory seizures (n=3), neuropsychiatric symptoms (n=3), ataxia (n=2), and anti-GAD autoantibodies were elevated in both the serum and cerebrospinal fluid (n=3). All three cases tried several combinations of ASMs and immunotherapies before tocilizumab but they remained with refractory epilepsy. Following several cycles of the tocilizumab, all cases had significant positive changes: seizure freedom (n=1), seizure control (n=2), improved-normal cognition (n=3), improved neuropsychiatry symptoms (n=2) and controlled ataxia (n=2).</p><p><strong>Conclusion: </strong>Tocilizumab seems to be an effective therapy for the refractory anti-GAD65 related epilepsy as it can control seizures, improve cognition and neuropsychiatric symptoms.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"491-500"},"PeriodicalIF":6.2,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12013633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144041922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integration of scRNA-Seq and Bulk RNA-Seq Identifies Circadian Rhythm Disruption-Related Genes Associated with Prognosis and Drug Resistance in Colorectal Cancer Patients.","authors":"Yong Tao, Jun Li, Jianhui Pan, Qing Wang, Ru Wei Ke, Danping Yuan, Hongbiao Wu, Yuepeng Cao, Lei Zhao","doi":"10.2147/ITT.S499806","DOIUrl":"https://doi.org/10.2147/ITT.S499806","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide. With the increasing incidence of CRC, there is an urgent need for effective strategies for early diagnosis and treatment. Circadian rhythm, a natural biological clock, regulates various physiological processes, and its disruption has been implicated in the onset and progression of cancer. However, the specific roles of circadian rhythm-related genes (CRDGs) in CRC remain unclear.</p><p><strong>Methods: </strong>In this study, we analyzed the expression patterns of CRDGs in CRC using single-cell RNA sequencing (scRNA-seq) data and bulk RNA sequencing data from the GSE178318 dataset. We constructed a CRC prognostic model based on CRD scores. Additionally, we explored the potential mechanisms of CRDGs in tumor progression through weighted gene co-expression network analysis (WGCNA) and gene set enrichment analysis (GSEA), and assessed their impact on the response to immune checkpoint inhibitors.</p><p><strong>Results: </strong>The analysis revealed that CRDGs were significantly upregulated in liver metastasis samples compared to primary CRC samples and were closely associated with several metabolic and immune-related pathways. The prognostic model based on CRD scores indicated that higher CRD scores were associated with poorer outcomes in immunotherapy. These findings were further validated in multiple datasets, underscoring the potential of CRDGs as prognostic indicators in CRC.</p><p><strong>Conclusion: </strong>This study systematically reveals, for the first time, the expression characteristics of CRDGs in CRC and their relationship with tumor progression and response to immunotherapy. CRDGs may serve as effective prognostic biomarkers and therapeutic targets, offering new strategies for the personalized treatment of CRC.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"475-489"},"PeriodicalIF":6.2,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12000913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144052781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective Deletion of HLA-B, and -C Class I Genes Promotes Immunocompatibility of Humanized Skin Graft Model.","authors":"Laura Cobos-Figueroa, Laura Notario, Carmen Mir, Carlos Molpeceres, Sara Lauzurica, Daniel López, Elena Lorente, Pilar Lauzurica","doi":"10.2147/ITT.S506352","DOIUrl":"https://doi.org/10.2147/ITT.S506352","url":null,"abstract":"<p><strong>Background: </strong>The treatment of extensive burns requires rapid allogeneic skin transplantation, but HLA diversity poses a significant challenge in finding histocompatible donor-recipient matches.</p><p><strong>Methods: </strong>In this study, we developed a humanized skin graft model using HLA class I transgenic mice to closely examine the HLA-mediated immune response in skin transplantation. Additionally, this model was used to analyse the response against a human lymphoblastoid cell line, JY, with HLA-B and -C genes knocked out by a single-step CRISPR-Cas9 strategy, retaining the most common HLA class I allele, HLA-A*02:01.</p><p><strong>Results: </strong>Mice expressing the HLA-A02:01 allele alone or in combination with HLA-B07:02 do not reject the skin of animals expressing only HLA-A02:01. However, skin from HLA-A02:01/B07:02 mice transplanted into HLA-A02:01 mice is rejected, triggering a strong specific CD8 T cell response mediated by the HLA-B*07:02 molecule. In these latter mice, unlike the parental JY cell line, the edited cells did not induce a CD8 T cell response in vitro, suggesting that the selective deletion of HLA-B and -C may contribute to improve skin graft compatibility.</p><p><strong>Conclusion: </strong>This genetic engineering approach, repeated without modification for the five HLA-A class I most common alleles known to be associated with HLA-B7 and -C7 in the same haplotype, would cover 83.4% of the world population. Our findings offer a scalable HLA-compatible skin graft model, potentially improving practices in burn units worldwide.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"451-463"},"PeriodicalIF":6.2,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11994478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143988184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Case Series of Anti-Metabotropic Glutamate Receptor 2 Antibody-Related Diseases with Distinct Neurological Involvement.","authors":"Zhanwei Zhang, Xiaolu Deng, Dandan Guo, Jie Zhao, Jian Li, Fang He, Lifen Yang, Jing Peng","doi":"10.2147/ITT.S514617","DOIUrl":"https://doi.org/10.2147/ITT.S514617","url":null,"abstract":"<p><strong>Background: </strong>Anti-metabotropic glutamate receptor 2 (mGluR2)-related diseases are rare autoimmune disorders of the central nervous system that primarily affect the cerebellum and are occasionally associated with malignancies.</p><p><strong>Methods: </strong>Data, including demographics, symptoms, blood and cerebrospinal fluid (CSF) tests, and brain magnetic resonance imaging (MRI), were retrospectively collected from two patients with informed consent at Xiangya Hospital from February 2024 to October 2024. Autoantibodies associated with autoimmune encephalitis were tested using cell-based assays. The literature describing anti-mGluR2 antibody-related diseases was searched for in PubMed and five cases were reviewed.</p><p><strong>Results: </strong>Two cases of anti-mGluR2 antibody-related diseases were reported: one with acute cerebellitis and the other with refractory seizures. Brain MRI showed cerebellar involvement in the cerebellitis patient. Anti-mGluR2 antibodies were detected in the serum but not in the CSF of both cases, and both responded well to immunotherapy. A review of five patients (all female, aged 3-78 years) found four with cerebellar ataxia or cerebellitis and one with immune-related epilepsy. Common symptoms included dysarthria, gait instability, and gaze/nystagmus, while seizures were rare. MRI revealed cerebellar involvement in most cases. Anti-mGluR2 antibodies were present in the serum of all patients but only in the CSF of two. Three patients responded well to immunosuppressive treatment, and two had malignancies.</p><p><strong>Conclusion: </strong>Anti-mGluR2 antibody-related diseases are autoimmune disorders primarily characterized by ataxic manifestations, though seizures may also occur. The effectiveness of immunosuppressive treatment is uncertain and screening for tumors is necessary.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"465-474"},"PeriodicalIF":6.2,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11994105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144022129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recombinant Antithrombin Alleviated Pulmonary Injury and Inflammation in LPS-Induced ARDS by Inhibiting IL17a/NF-κB Signaling.","authors":"Chen Yang, Cong Fu, Mengxue Wang, Junbo Zheng, Yang Gao, Huiting Zhu, Haoxuan Li, Dongxu Li, Lichen Guo, Bing Yu, Qingqing Dai","doi":"10.2147/ITT.S502925","DOIUrl":"https://doi.org/10.2147/ITT.S502925","url":null,"abstract":"<p><strong>Background: </strong>Recombinant antithrombin (rAT) has been shown to protect lungs from ARDS and modulate immune responses, but its anti-inflammatory mechanisms remain unclear. This study aimed to explore the immunomodulatory effects and mechanisms of rAT in LPS-induced ARDS mice.</p><p><strong>Methods: </strong>ARDS mouse model was established by intraperitoneally administration of 20 mg/kg LPS. After 3 hours of LPS administration, rAT or PBS was injected intravenously. Lung injury, alveolar permeability, serum inflammatory cytokines, immune cell infiltration in lung tissue, and the proportion of Th17 were assessed 36 hours after rAT administration. The functional roles of the differential expressed genes (DEGs), obtained from LPS-induced ARDS mice treated with or without rAT, were analyzed by GO, KEGG and GSEA enrichment analysis. The activation of NF-κB and NLRP3 inflammasome was evaluated by Western blot and immunofluorescence staining.</p><p><strong>Results: </strong>We found that rAT alleviated lung injury, reduced pulmonary permeability, decreased serum inflammatory cytokines, and suppressed immune cell infiltration and NLRP3 inflammasome activation. Moreover, rAT decreased the proportion of Th17 cells in lung tissues and peripheral blood, downregulated IL17a expression, and inhibited NF-κB signaling pathway in lung tissues. Additionally, the administration of IL-17A diminished the efficacy of rAT in mitigating lung injury, suppressing the immune response, and inhibiting the activation of the NF-κB signaling pathway in LPS-induced ARDS mice.</p><p><strong>Conclusion: </strong>The findings of this study suggest that rAT alleviates lung injury and suppresses inflammatory responses by inhibiting the IL17a/NF-κB signaling axis, suggesting that rAT may serve as a potential therapeutic agent for mitigating pulmonary inflammation and improving the prognosis of ARDS induced by sepsis. Furthermore, this study provides important research data and theoretical basis for the clinical translation and application of rAT.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"14 ","pages":"433-449"},"PeriodicalIF":6.2,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11988198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144054046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}