Yongyao Wu, Lilan He, Rong Li, Jiuxuan Li, Qing Zhao, Bin Shao
{"title":"A20 as a Potential Therapeutic Target for COVID-19","authors":"Yongyao Wu, Lilan He, Rong Li, Jiuxuan Li, Qing Zhao, Bin Shao","doi":"10.1002/iid3.70127","DOIUrl":"10.1002/iid3.70127","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a major concern due to its astonishing prevalence and high fatality rate, especially among elderly people. Patients suffering from COVID-19 may exhibit immunosuppression in the initial stage of infection, while a cytokine storm can occur when the disease progresses to a severe stage. This inopportune immune rhythm not only makes patients more susceptible to the virus but also leads to numerous complications resulting from the excessive production of inflammatory factors. A20, which is widely accepted as a pivotal regulator of inflammation, has been shown to be implicated in the processes of antiviral responses and immunosuppression. Thus, A20 may participate in regulating the pathological processes of COVID-19.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This narrative literature review summarizes recent evidence on the mechanisms of A20 in regulating the pathological processes of COVID-19. We also downloaded single-cell RNA-seq data sets from healthy individuals and patients with varying severities of COVID-19 from the NCBI GEO database to further dissect A20's regulatory mechanisms of these intricate cytokine pathways that are closely associated with SARS-CoV-2 infection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A20 might be one of the most critical anti-infectious and anti-inflammatory factors involved in the pathogenesis of COVID-19. It effectively suppresses the immune damage and inflammatory storm caused by viral infection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Understanding the relationship between A20-regulated signaling pathways and pathological processes of COVID-19 can provide insight into potential targets for intervention. Precise regulation of A20 to induce antiviral activity and an anti-inflammatory response could mediate the pathogenesis of COVID-19 and could become an effective treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143033103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Serum Alkaline Phosphatase Levels in Pediatric Kikuchi-Fujimoto Disease: A Retrospective Observational Analysis","authors":"Shintaro Fujiwara, Yousuke Higuchi, Junya Shimizu","doi":"10.1002/iid3.70129","DOIUrl":"10.1002/iid3.70129","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Kikuchi-Fujimoto disease (KFD) rarely affects pediatric patients and is characterized by prolonged fever and cervical lymphadenopathy. The diagnosis of KFD remains challenging and often requires an invasive biopsy. Low serum alkaline phosphatase levels have frequently been observed in patients with KFD; however, the clinical significance of low serum alkaline phosphatase levels remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This retrospective study included pediatric patients aged < 16 years who were pathologically or clinically diagnosed with KFD and infectious mononucleosis between April 2016 and March 2023. Serum alkaline phosphatase levels were analyzed employing age- and sex-specific reference intervals. Clinical and laboratory data were evaluated to determine their association with serum alkaline phosphatase levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Thirty patients with KFD and 23 patients with infectious mononucleosis were included in the study. Seventeen patients with KFD (56.7%) had serum alkaline phosphatase levels below the 2.5th percentile of the age- and sex-specific reference intervals. Serum alkaline phosphatase levels were significantly lower in patients with KFD than in those with infectious mononucleosis. Clinical and other laboratory findings were not significantly different between patients with KFD with or without a decline in serum alkaline phosphatase levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>A decrease in serum alkaline phosphatase levels, particularly when assessed as a percentage of age- and sex-specific reference intervals, may be a valuable and noninvasive supportive feature of KFD in pediatric patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yiming Shi, Yingying Qin, Yunshen Li, Ping Jiang, Kai Wei, Jianan Zhao, Yu Shan, Yixin Zheng, Fuyu Zhao, Mi Zhou, Li Li, Yu Shen, Xinliang Lv, Yuejuan Zheng, Shicheng Guo, Qin Ding, Cen Chang, Dongyi He
{"title":"Comparative Analysis of CXCR5 Circulating DNA Methylation Levels in Autoimmune Rheumatic Diseases","authors":"Yiming Shi, Yingying Qin, Yunshen Li, Ping Jiang, Kai Wei, Jianan Zhao, Yu Shan, Yixin Zheng, Fuyu Zhao, Mi Zhou, Li Li, Yu Shen, Xinliang Lv, Yuejuan Zheng, Shicheng Guo, Qin Ding, Cen Chang, Dongyi He","doi":"10.1002/iid3.70128","DOIUrl":"10.1002/iid3.70128","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To assess CXC chemokine receptor 5 (CXCR5) circulating DNA methylation differences in autoimmune rheumatic diseases and their relation with clinical features.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Targeted methylation sequencing was performed using peripheral blood from 164 rheumatoid arthritis (RA), 30 systemic lupus erythematosus (SLE), 30 ankylosing spondylitis (AS), 30 psoriatic arthritis (PsA), 24 Sjögren's syndrome (SS) patients, and 30 healthy controls (HC).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Significant differences in CXCR5 cg19599951 methylation were found between RA and HC, as well as AS and SLE. RA patients exhibited higher methylation than HC and AS (<i>p</i> < 0.01) but lower than SLE (<i>p</i> < 0.05). SLE patients showed higher methylation compared to HC, AS, and PsA (<i>p</i> < 0.001, 0.01, and 0.05, respectively). No significant differences were found in patients with SS compared to other autoimmune diseases and HC. Methylation at cg19599951_103 (<i>r</i> = 0.17, <i>p</i> < 0.05) and cg19599951_209 (<i>r</i> = 0.22, <i>p</i> < 0.01), along with the CC haplotype (<i>r</i> = 0.21, <i>p</i> < 0.01), showed significant positive correlations with erythrocyte sedimentation rate (ESR), while the CT (<i>r</i> = −0.27, <i>p</i> < 0.001) and TT haplotypes (<i>r</i> = −0.19, <i>p</i> < 0.05) were negatively correlated. For C-reactive protein (CRP), methylation at cg19599951_103 (<i>r</i> = 0.29, <i>p</i> < 0.001) and cg19599951_209 (<i>r</i> = 0.33, <i>p</i> < 0.0001), and the CC haplotype (<i>r</i> = 0.34, <i>p</i> < 0.0001) was positively correlated, whereas the CT (<i>r</i> = −0.36, <i>p</i> < 0.0001) and TT (<i>r</i> = −0.30, <i>p</i> < 0.0001) haplotypes were negatively correlated. Significant negative correlations were observed between the CT haplotype and rheumatoid factor (<i>r</i> = −0.25, <i>p</i> < 0.01), and anti-citrullinated protein antibody (<i>r</i> = −0.20, <i>p</i> < 0.05). No significant correlations were found in patients with SLE, AS, and SS. Receiver operating characteristic analysis showed CXCR5 methylation could classify patients with RA versus those with AS (AUC: 0.624−0.967).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Differential circulating CXCR5 methylation levels were observed in autoimmune rheumatic diseases, which correlated with inflammatory mediators in RA and may serve as potential biomarkers for RA diagnosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Histogram of Apparent Diffusion Coefficient to Evaluate the Activity of Thyroid-Associated Ophthalmopathy","authors":"Defu Li, Tingting Zhu, Yujin Wang","doi":"10.1002/iid3.70131","DOIUrl":"10.1002/iid3.70131","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aimed to evaluate the activity of extraocular muscles (EOMs) in patients with thyroid-associated ophthalmopathy (TAO) using turbo spin echo imaging. By analyzing tissue heterogeneity, apparent diffusion coefficient (ADC) histogram analysis offers enhanced insights into edema within the EOMs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Eighty-eight patients with TAO were retrospectively evaluated and allocated into active (<i>n</i> = 24, clinical activity score [CAS] ≥ 3) and inactive (<i>n</i> = 64, CAS < 3) groups. The parameter values of the ADC histogram of EOMs were measured; the efficacy of ADC histograms in distinguishing between TAO activity and inactivity was assessed using receiver operating characteristic curves. Multifactorial logistic regression was used to determine active TAO predictors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The minimum, maximum, median, mean; and 1st, 5th, 10th, 25th, 75th, 90th, 95th, and 99th percentiles of the ADC histograms were higher in patients with active than that in participants with inactive TAO. The area under the curve (AUC) of the 10th percentile of the ADC histogram and the median distinguishing between active and inactive TAOs were both 0.791 (both <i>p</i> < 0.05), and the AUCs of the combined model of age, sex, smoking, and the 10th percentile in the ADC histogram were better than those of their individual models and the combined model of age, sex, and smoking (all <i>p</i> < 0.05). Smoking and male sex, along with the median > 1.26 μm<sup>2</sup>/s, entropy > 4.03, and standard deviation (SD) > 0.4 of the ADC histogram, were significant predictors of TAO activity, with odds ratios of 2.741 and 6.806, 5.070, 2.652, and 2.197, respectively (all <i>p</i> < 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>ADC histograms provide a new method for distinguishing active from inactive TAO, and the 10th percentile enhances the clinical diagnosis of active TAO. In addition to male sex and smoking, an ADC histogram median > 1.26 μm²/s, entropy > 4.03, or SD > 0.4 may also predict active TAO.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yuyun Zhong, Ruiqi Wang, Zijie Huang, Zhaoting Hu, Bin Peng, Bin Chen, Liyue Sun
{"title":"Identification of SETD4 as an Onco-Immunological Biomarker Encompassing the Tumor Microenvironment, Prognoses, and Therapeutic Responses in Various Human Cancers","authors":"Yuyun Zhong, Ruiqi Wang, Zijie Huang, Zhaoting Hu, Bin Peng, Bin Chen, Liyue Sun","doi":"10.1002/iid3.70126","DOIUrl":"10.1002/iid3.70126","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>SET domain-containing protein 4 (SETD4) is a histone methyltransferase that has been shown to modulate cell proliferation, differentiation, and inflammatory responses by regulating histone H4 trimethylation (H4K20me3). Previous reports have demonstrated its function in the quiescence of cancer stem cells as well as drug resistance in several cancers. A limited number of systematic studies have examined SETD4's role in the tumor microenvironment, pathogenesis, prognosis, and therapeutic response.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Utilizing The Cancer Genome Atlas database, and other publicly accessible platforms, we comprehensively analyzed SETD4 gene expression, methylation patterns, and prognostic significance. Furthermore, we investigated its association with cancer-related pathways, the immune microenvironment, immunotherapy markers, and drug resistance signatures of chemotherapy. Additionally, qRT-PCR was performed to validate SETD4 expression in clinical specimens.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The expression of SETD4 was abnormal across a variety of cancer types and the expression of SETD4 in colorectal cancer tissues was verified in clinical specimens. The upregulation of SETD4 may be a prognostic risk factor predicting poor overall survival and progression-free survival. The analysis revealed that the mRNA level of SETD4 was modulated by promoter methylation, and patients with lower methylation levels showed shorter survival times. Pathway analysis showed that SETD4 influenced several key cell cycle pathways, including the G2M checkpoint, and mitotic spindle pathways. In addition, SETD4 negatively affects immune cell infiltration in most cancers, including B cells, CD8 T cells, and macrophages. The correlation between SETD4 and cancer stemness as well as homologous recombination deficiency varied across tumor types, suggesting that SETD4 may play a multifaceted role in tumor resistance. Notably, we identified several potential agents targeting SETD4.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study demonstrates that SETD4 is an immune-oncogenic molecule in multiple cancers, with the potential to be a diagnosis, prognosis, and targeted therapy marker.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11736640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Muhammad Osama Siddiqui, Mohammad Ali Syed, Ayaan Ahmed Qureshi, Mustafa Hussain Imam, Jatin Motwani, Verkha Kumari, Arooba Siddiqui, Noor Ul Ain, Mohammed Hammad Jaber
{"title":"Risk Factors and Pharmacological Interventions Impacting Cerebrovascular Ischemic Events in Giant Cell Arteritis: A Narrative Review","authors":"Muhammad Osama Siddiqui, Mohammad Ali Syed, Ayaan Ahmed Qureshi, Mustafa Hussain Imam, Jatin Motwani, Verkha Kumari, Arooba Siddiqui, Noor Ul Ain, Mohammed Hammad Jaber","doi":"10.1002/iid3.70122","DOIUrl":"10.1002/iid3.70122","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Giant cell arteritis (GCA) is a common vasculitis predominantly affecting larger vessels, especially in individuals aged 70–79. Cerebrovascular ischemic events (CIE), such as stroke and transient ischemic attacks, are serious but rare complications of GCA, with a pooled prevalence of 4%. Some studies found that within 2 weeks of GCA diagnosis, 74% and 34% of patients experience transient or severe ischemic events, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Our study aims to help physicians better manage GCA patients to reduce GCA-related CIE by indicating important risk factors and pharmacological intervention to prevent GCA-related CIE, particularly in the first few days of diagnosis when the risk of CIE is highest.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A comprehensive literature search was conducted using Pubmed, Google Scholar, Scopus, and other relevant medical databases. As this study was a narrative review, the literature search was done in a nonsystematic manner. Studies published from 2000 to 2024 were reviewed in a nonsystematic manner for information on incidence, pathology, risk factors, pharmacological intervention, and management of GCA-related CIE.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Findings indicate that age, male gender, hypertension, and smoking significantly increase the risk of GCA-related CIE, while factors such as anemia, higher body mass index (BMI), and elevated inflammatory markers (C-reactive protein [CRP] and erythrocyte sedimentation rate [ESR]) appear to have protective effects. Symptoms of ischemia in the ophthalmic artery were identified as the strongest predictors of CIE. Pharmacological treatments, including glucocorticoids and tocilizumab, are instrumental in managing and potentially preventing CIE in GCA patients, with adjunctive therapies such as aspirin and antiplatelet agents also showing promise.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>GCA-related CIE such as stroke can be very debilitating and deadly conditions, particularly when GCA is initially diagnosed. However, with early diagnosis and proper management of risk factors, GCA-related CIE can be prevented and its severity can be reduced. Ischemia in the ophthalmic artery is found to strongly predict GCA-related CIE while aspirin and antiplatelet agent during the first 3 months may prevent GCA-related CIE. Risk factors such as BMI and smoking may help in stratifying the risk o","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11736630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sara Gangi, Laura Bergantini, Irene Paggi, Marco Spalletti, Paolo Cameli, Elena Bargagli, Miriana d'Alessandro
{"title":"Regulatory T Cell Phenotype Related to Cytokine Expression Patterns in Post-COVID-19 Pulmonary Fibrosis and Idiopathic Pulmonary Fibrosis","authors":"Sara Gangi, Laura Bergantini, Irene Paggi, Marco Spalletti, Paolo Cameli, Elena Bargagli, Miriana d'Alessandro","doi":"10.1002/iid3.70123","DOIUrl":"10.1002/iid3.70123","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Post-coronavirus disease 19 lung fibrosis (PCLF) shares common immunological abnormalities with idiopathic pulmonary fibrosis (IPF), characterized by an unbalanced cytokine profile being associated with the development of lung fibrosis. The aim of the present study was to analyze and compare the different subsets of CD4- and CD8-T cells, along with specific cytokine expression patterns, in peripheral blood (PB) from patients affected by PCLF and IPF and healthy controls (HCs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>One-hundred patients followed at the Rare Lung Disease Center of Siena University Hospital were enrolled. Eight HCs were recruited. PB samples were collected, and CD4- and CD8-T subsets were analyzed through flow cytometry. Multiplex bead-based LEGENDplex™ were used for cytokine quantification.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Higher CD8 percentages were observed in IPF than in HCs and PCLF (<i>p</i> = 0.020 and <i>p</i> = 0.007, respectively). PCLF subgroup showed higher Th-naïve, Th-effector, Tc-naïve, and Tc-reg percentages than IPF (<i>p</i> < 0.001; <i>p</i> = 0.018; <i>p</i> = 0.005; <i>p</i> = 0.017, respectively). Th-naïve and Tc-naïve inversely correlated with Tc-reg (<i>p</i> < 0.0001, <i>r</i> = −0.61 and <i>p</i> = 0.005, <i>r</i> = −0.39, respectively). Tc-naïve-PD1 and Tc-effector-PD1 percentages were higher in PCLF than IPF (<i>p</i> < 0.001), while Tfh-reg and Tfc-reg were significantly higher in IPF than PCLF (<i>p</i> < 0.001). IL-4, IL-2, TNF-α, and IL-17A were more expressed in PCLF than IPF (<i>p</i> < 0.001). IL-8 directly correlated with Tc-naïve percentages in PCLF (<i>p</i> = 0.018, <i>r</i> = 0.35).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>A variety of immune cells is involved in the development and progression of pulmonary fibrosis confirming an immunological similarity between IPF and PCLF. T-reg cells play a key role in the worsening of the disease. High cytokine values showed a pro-fibrotic environment in PCLF patients, suggesting dysregulation of the immune system of these patients. Moreover, the immunological similarity between IPF and PCLF patients suggests that SARS-CoV2 infection may trigger the activation of biological pathways common with IPF.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11729443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142978325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Protective Effects of Annexin A1 in Acute Lung Injury Mediated by Nrf2","authors":"Hui Huang, Yuqin Shi, Yuequan Zhou","doi":"10.1002/iid3.70111","DOIUrl":"10.1002/iid3.70111","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Acute lung injury (ALI), one of the most severe respiratory system diseases, is prevalent worldwide. Annexin A1 (AnxA1) is an important member of the annexin superfamily, known for its wide range of physiological functions. However, its potential protective effect against lipopolysaccharide (LPS)-induced ALI remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>Mice were divided into four groups: Sham, LPS + vehicle, LPS + 0.1 μg AnxA1, and LPS + 0.5 μg AnxA1. Lung injury was assessed through histopathology, pulmonary wet-to-dry (W/D) ratio, cell counting of bronchoalveolar lavage fluid (BALF), oxidative stress analysis, and noninvasive pulmonary function testing. Gene and protein expression levels were measured using RT-PCR, ELISA, and western blot analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>AnxA1 alleviated LPS-induced ALI by protecting lung tissue from damage, reducing the lung wet/dry (W/D) weight ratio, and improving LPS-induced impaired lung function. Interestingly, administration of AnxA1 was found to repress the infiltration of inflammatory cells by decreasing the total cell count, neutrophils, and protein concentrations in bronchoalveolar lavage fluid (BALF). AnxA1 mitigated the inflammatory response in the pulmonary tissue by lowering the levels of IL-1β, IL-6, and TNF-α in BALF of ALI mice. Additionally, AnxA1 attenuated oxidative stress in lung tissues of ALI mice by restoring the activity of catalase (CAT), SOD, and glutathione (GSH) but reducing the levels of malondialdehyde (MDA). We also found that AnxA1 suppressed activation of the NLRP3 signaling pathway. Mechanistically, AnxA1 activated the Nrf2/HO-1 signaling pathway while preventing the activation of NF-κB.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Collectively, these findings suggest that AnxA1 alleviates LPS-induced ALI and might be a promising novel therapeutic agent against LPS-induced ALI.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11729740/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142978326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to “NR5A2 Promotes Malignancy Progression and Mediates the Effect of Cisplatin in Cutaneous Squamous Cell Carcinoma”","authors":"","doi":"10.1002/iid3.70125","DOIUrl":"10.1002/iid3.70125","url":null,"abstract":"<p>W. Ye, C. Ya-Xuan, T. Shan-Shan, L. Qiu, M. Ting, C. Shao-Jie, and C. Yu, “NR5A2 Promotes Malignancy Progression and Mediates the Effect of Cisplatin in Cutaneous Squamous Cell Carcinoma,” <i>Immunity, Inflammation and Disease</i> 12, no. 2 (2024): e1172, https://doi.org/10.1002/iid3.1172.</p><p>In the original version of this paper, the images in the wound healing experiment for two cell lines were inadvertently duplicated in Figure 4D. The authors have since reviewed the original scans and repeated the experiment. The figures have been corrected accordingly, and this revision does not impact the conclusions of the article in any way. The corrected Figure 4 is shown below. We apologize for this error.</p>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11729373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142978324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"NRF2 Antioxidant Response and Interferon-Stimulated Genes Are Differentially Expressed in SARS-CoV-2-Positive Young Subjects","authors":"Toscanelli Walter, Fracella Matteo, De Angelis Marta, Scagnolari Carolina, Sorrentino Leonardo, Piselli Elena, Marcocci Maria Elena, Midulla Fabio, Mancino Enrica, Nenna Raffaella, Petrarca Laura, Palamara Anna Teresa, Antonelli Guido, Pierangeli Alessandra, Nencioni Lucia","doi":"10.1002/iid3.70109","DOIUrl":"10.1002/iid3.70109","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Several respiratory viruses, including Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2), suppress nuclear factor-E2-related factor-2 (NRF2) antioxidant response, generating oxidative stress conditions to its advantage. NRF2 has also been reported to regulate the innate immune response through the inhibition of the interferon (IFN) pathway. However, its modulation in younger individuals and its correlation with the IFN response remain to be elucidated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The NRF2 and redox-related genes expression was examined in nasopharyngeal swabs from children attending the pediatric hospital for SARS-CoV-2 molecular testing. Expression levels were analyzed by stratifying the population according to the SARS-CoV-2 positivity, age, or the presence of symptoms. The results were correlated with Types I and III IFN genes and IFN-stimulated genes (ISGs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found that NRF2 expression was markedly diminished in positive patients compared to negative. Moreover, it correlated with higher expression of IFNα2 and IFNλ3, as well as ISG15 and ISG56. Interestingly, symptomatic patients with anosmia/ageusia showed pronounced expression of apurinic/apyrimidinic endonuclease1/redox factor 1 (APE1), together with Type I IFNs, ISG56, and the inflammasome component NLRP3.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The results indicate an interdependence between NRF2 antioxidant pathway and IFN-mediated response during SARS-CoV-2 infection in young subjects.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11733084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}