Immune Network最新文献_第6页

Comprehensive Transcriptomic Analysis for Thymic Epithelial Cells of Aged Mice and Humans. 老年小鼠和人胸腺上皮细胞的综合转录组学分析。

IF 6 4区医学

Immune Network Pub Date : 2023-08-21 eCollection Date: 2023-10-01 DOI: 10.4110/in.2023.23.e36

Sangsin Lee, Seung Geun Song, Doo Hyun Chung

{"title":"Comprehensive Transcriptomic Analysis for Thymic Epithelial Cells of Aged Mice and Humans.","authors":"Sangsin Lee, Seung Geun Song, Doo Hyun Chung","doi":"10.4110/in.2023.23.e36","DOIUrl":"https://doi.org/10.4110/in.2023.23.e36","url":null,"abstract":"Thymic epithelial cells (TECs) play a critical role in thymic development and thymopoiesis. As individuals age, TECs undergo various changes that impact their functions, leading to a reduction in cell numbers and impaired thymic selection. These age-related alterations have been observed in both mice and humans. However, the precise mechanisms underlying age-related TEC dysfunction remain unclear. Furthermore, there is a lack of a comprehensive study that connects mouse and human biological processes in this area. To address this gap, we conducted an extensive transcriptome analysis of young and old TECs in mice, complemented by further analysis of publicly available human TEC single-cell RNA sequencing data. Our analysis revealed alterations in both known and unknown pathways that potentially contribute to age-related TEC dysfunction. Specifically, we observed downregulation of pathways related to cell proliferation, T cell development, metabolism, and cytokine signaling in old age TECs. Conversely, TGF-β, BMP, and Wnt signaling pathways were upregulated, which have been known to be associated with age-related TEC dysfunctions or newly discovered in this study. Importantly, we found that these age-related changes in mouse TECs were consistently present in human TECs as well. This cross-species validation further strengthens the significance of our findings. In conclusion, our comprehensive analysis provides valuable insight into the biological and immunological characteristics of aged TECs in both mice and humans. These findings contribute to a better understanding of thymic involution and age-induced immune dysfunction.","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"23 5","pages":"e36"},"PeriodicalIF":6.0,"publicationDate":"2023-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10643332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134648813","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}

引用次数: 0

Vaccine Strategy That Enhances the Protective Efficacy of Systemic Immunization by Establishing Lung-Resident Memory CD8 T Cells Against Influenza Infection. 通过建立针对流感感染的肺驻留记忆 CD8 T 细胞来增强全身免疫保护效力的疫苗策略。

IF 4.3 4区医学

Immune Network Pub Date : 2023-08-04 eCollection Date: 2023-08-01 DOI: 10.4110/in.2023.23.e32

Hyun-Jung Kong, Youngwon Choi, Eun-Ah Kim, Jun Chang

{"title":"Vaccine Strategy That Enhances the Protective Efficacy of Systemic Immunization by Establishing Lung-Resident Memory CD8 T Cells Against Influenza Infection.","authors":"Hyun-Jung Kong, Youngwon Choi, Eun-Ah Kim, Jun Chang","doi":"10.4110/in.2023.23.e32","DOIUrl":"10.4110/in.2023.23.e32","url":null,"abstract":"Most influenza vaccines currently in use target the highly variable hemagglutinin protein to induce neutralizing antibodies and therefore require yearly reformulation. T cell-based universal influenza vaccines focus on eliciting broadly cross-reactive T-cell responses, especially the tissue-resident memory T cell (TRM) population in the respiratory tract, providing superior protection to circulating memory T cells. This study demonstrated that intramuscular (i.m.) administration of the adenovirus-based vaccine expressing influenza virus nucleoprotein (rAd/NP) elicited weak CD8 TRM responses in the lungs and airways, and yielded poor protection against lethal influenza virus challenge. However, a novel \"prime-and-deploy\" strategy that combines i.m. vaccination of rAd/NP with subsequent intranasal administration of an empty adenovector induced strong NP-specific CD8+ TRM cells and provided complete protection against influenza virus challenge. Overall, our results demonstrate that this \"prime-and-deploy\" vaccination strategy is potentially applicable to the development of universal influenza vaccines.","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"23 4","pages":"e32"},"PeriodicalIF":4.3,"publicationDate":"2023-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ef/d9/in-23-e32.PMC10475829.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10160205","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}

引用次数: 0

A Moonlighting Protein Secreted by a Nasal Microbiome Fortifies the Innate Host Defense Against Bacterial and Viral Infections. 鼻腔微生物组分泌的一种 "月光蛋白 "可增强宿主对细菌和病毒感染的先天防御能力

IF 4.3 4区医学

Immune Network Pub Date : 2023-08-03 eCollection Date: 2023-08-01 DOI: 10.4110/in.2023.23.e31

Gwanghee Kim, Yoojin Lee, Jin Sun You, Wontae Hwang, Jeewon Hwang, Hwa Young Kim, Jieun Kim, Ara Jo, In Ho Park, Mohammed Ali, Jongsun Kim, Jeon-Soo Shin, Ho-Keun Kwon, Hyun Jik Kim, Sang Sun Yoon

{"title":"A Moonlighting Protein Secreted by a Nasal Microbiome Fortifies the Innate Host Defense Against Bacterial and Viral Infections.","authors":"Gwanghee Kim, Yoojin Lee, Jin Sun You, Wontae Hwang, Jeewon Hwang, Hwa Young Kim, Jieun Kim, Ara Jo, In Ho Park, Mohammed Ali, Jongsun Kim, Jeon-Soo Shin, Ho-Keun Kwon, Hyun Jik Kim, Sang Sun Yoon","doi":"10.4110/in.2023.23.e31","DOIUrl":"10.4110/in.2023.23.e31","url":null,"abstract":"Evidence suggests that the human respiratory tract, as with the gastrointestinal tract, has evolved to its current state in association with commensal microbes. However, little is known about how the airway microbiome affects the development of airway immune system. Here, we uncover a previously unidentified mode of interaction between host airway immunity and a unique strain (AIT01) of Staphylococcus epidermidis, a predominant species of the nasal microbiome. Intranasal administration of AIT01 increased the population of neutrophils and monocytes in mouse lungs. The recruitment of these immune cells resulted in the protection of the murine host against infection by Pseudomonas aeruginosa, a pathogenic bacterium. Interestingly, an AIT01-secreted protein identified as GAPDH, a well-known bacterial moonlighting protein, mediated this protective effect. Intranasal delivery of the purified GAPDH conferred significant resistance against other Gram-negative pathogens (Klebsiella pneumoniae and Acinetobacter baumannii) and influenza A virus. Our findings demonstrate the potential of a native nasal microbe and its secretory protein to enhance innate immune defense against airway infections. These results offer a promising preventive measure, particularly relevant in the context of global pandemics.","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"23 4","pages":"e31"},"PeriodicalIF":4.3,"publicationDate":"2023-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/34/09/in-23-e31.PMC10475824.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10160206","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}

引用次数: 0

SARS-CoV-2 mRNA Vaccine Elicits Sustained T Cell Responses Against the Omicron Variant in Adolescents. SARS-CoV-2 mRNA疫苗在青少年中引发针对组粒变异的持续T细胞反应

IF 6 4区医学

Immune Network Pub Date : 2023-08-01 DOI: 10.4110/in.2023.23.e33

Sujin Choi, Sang-Hoon Kim, Mi Seon Han, Yoonsun Yoon, Yun-Kyung Kim, Hye-Kyung Cho, Ki Wook Yun, Seung Ha Song, Bin Ahn, Ye Kyung Kim, Sung Hwan Choi, Young June Choe, Heeji Lim, Eun Bee Choi, Kwangwook Kim, Seokhwan Hyeon, Hye Jung Lim, Byung-Chul Kim, Yoo-Kyoung Lee, Eun Hwa Choi, Eui-Cheol Shin, Hyunju Lee

{"title":"SARS-CoV-2 mRNA Vaccine Elicits Sustained T Cell Responses Against the Omicron Variant in Adolescents.","authors":"Sujin Choi, Sang-Hoon Kim, Mi Seon Han, Yoonsun Yoon, Yun-Kyung Kim, Hye-Kyung Cho, Ki Wook Yun, Seung Ha Song, Bin Ahn, Ye Kyung Kim, Sung Hwan Choi, Young June Choe, Heeji Lim, Eun Bee Choi, Kwangwook Kim, Seokhwan Hyeon, Hye Jung Lim, Byung-Chul Kim, Yoo-Kyoung Lee, Eun Hwa Choi, Eui-Cheol Shin, Hyunju Lee","doi":"10.4110/in.2023.23.e33","DOIUrl":"https://doi.org/10.4110/in.2023.23.e33","url":null,"abstract":"Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been acknowledged as an effective mean of preventing infection and hospitalization. However, the emergence of highly transmissible SARS-CoV-2 variants of concern (VOCs) has led to substantial increase in infections among children and adolescents. Vaccine-induced immunity and longevity have not been well defined in this population. Therefore, we aimed to analyze humoral and cellular immune responses against ancestral and SARS-CoV-2 variants after two shots of the BNT162b2 vaccine in healthy adolescents. Although vaccination induced a robust increase of spike-specific binding Abs and neutralizing Abs against the ancestral and SARS-CoV-2 variants, the neutralizing activity against the Omicron variant was significantly low. On the contrary, vaccine-induced memory CD4+ T cells exhibited substantial responses against both ancestral and Omicron spike proteins. Notably, CD4+ T cell responses against both ancestral and Omicron strains were preserved at 3 months after two shots of the BNT162b2 vaccine without waning. Polyfunctionality of vaccine-induced memory T cells was also preserved in response to Omicron spike protein. The present findings characterize the protective immunity of vaccination for adolescents in the era of continuous emergence of variants/subvariants.","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"23 4","pages":"e33"},"PeriodicalIF":6.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3c/42/in-23-e33.PMC10475828.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10166475","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}

引用次数: 0

Comprehensive Lipid Profiling Recapitulates Enhanced Lipolysis and Fatty Acid Metabolism in Intimal Foamy Macrophages From Murine Atherosclerotic Aorta. 综合脂质谱重现了小鼠动脉粥样硬化主动脉内膜泡沫巨噬细胞中脂肪分解和脂肪酸代谢的增强。

IF 6 4区医学

Immune Network Pub Date : 2023-08-01 DOI: 10.4110/in.2023.23.e28

Jae Won Seo, Kyu Seong Park, Gwang Bin Lee, Sang-Eun Park, Jae-Hoon Choi, Myeong Hee Moon

{"title":"Comprehensive Lipid Profiling Recapitulates Enhanced Lipolysis and Fatty Acid Metabolism in Intimal Foamy Macrophages From Murine Atherosclerotic Aorta.","authors":"Jae Won Seo, Kyu Seong Park, Gwang Bin Lee, Sang-Eun Park, Jae-Hoon Choi, Myeong Hee Moon","doi":"10.4110/in.2023.23.e28","DOIUrl":"https://doi.org/10.4110/in.2023.23.e28","url":null,"abstract":"Lipid accumulation in macrophages is a prominent phenomenon observed in atherosclerosis. Previously, intimal foamy macrophages (FM) showed decreased inflammatory gene expression compared to intimal non-foamy macrophages (NFM). Since reprogramming of lipid metabolism in macrophages affects immunological functions, lipid profiling of intimal macrophages appears to be important for understanding the phenotypic changes of macrophages in atherosclerotic lesions. While lipidomic analysis has been performed in atherosclerotic aortic tissues and cultured macrophages, direct lipid profiling has not been performed in primary aortic macrophages from atherosclerotic aortas. We utilized nanoflow ultrahigh-performance liquid chromatography-tandem mass spectrometry to provide comprehensive lipid profiles of intimal non-foamy and foamy macrophages and adventitial macrophages from Ldlr-/- mouse aortas. We also analyzed the gene expression of each macrophage type related to lipid metabolism. FM showed increased levels of fatty acids, cholesterol esters, phosphatidylcholine, lysophosphatidylcholine, phosphatidylinositol, and sphingomyelin. However, phosphatidylethanolamine, phosphatidic acid, and ceramide levels were decreased in FM compared to those in NFM. Interestingly, FM showed decreased triacylglycerol (TG) levels. Expressions of lipolysis-related genes including Pnpla2 and Lpl were markedly increased but expressions of Lpin2 and Dgat1 related to TG synthesis were decreased in FM. Analysis of transcriptome and lipidome data revealed differences in the regulation of each lipid metabolic pathway in aortic macrophages. These comprehensive lipidomic data could clarify the phenotypes of macrophages in the atherosclerotic aorta.","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"23 4","pages":"e28"},"PeriodicalIF":6.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/62/dc/in-23-e28.PMC10475825.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10171753","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}

引用次数: 0

CD5 Expression Dynamically Changes During the Differentiation of Human CD8⁺ T Cells Predicting Clinical Response to Immunotherapy. CD5表达在人CD8+ T细胞分化过程中的动态变化预测免疫治疗的临床反应

IF 6 4区医学

Immune Network Pub Date : 2023-08-01 DOI: 10.4110/in.2023.23.e35

Young Ju Kim, Kyung Na Rho, Saei Jeong, Gil-Woo Lee, Hee-Ok Kim, Hyun-Ju Cho, Woo Kyun Bae, In-Jae Oh, Sung-Woo Lee, Jae-Ho Cho

{"title":"CD5 Expression Dynamically Changes During the Differentiation of Human CD8+ T Cells Predicting Clinical Response to Immunotherapy.","authors":"Young Ju Kim, Kyung Na Rho, Saei Jeong, Gil-Woo Lee, Hee-Ok Kim, Hyun-Ju Cho, Woo Kyun Bae, In-Jae Oh, Sung-Woo Lee, Jae-Ho Cho","doi":"10.4110/in.2023.23.e35","DOIUrl":"https://doi.org/10.4110/in.2023.23.e35","url":null,"abstract":"Defining the molecular dynamics associated with T cell differentiation enhances our understanding of T cell biology and opens up new possibilities for clinical implications. In this study, we investigated the dynamics of CD5 expression in CD8+ T cell differentiation and explored its potential clinical uses. Using PBMCs from 29 healthy donors, we observed a stepwise decrease in CD5 expression as CD8+ T cells progressed through the differentiation stages. Interestingly, we found that CD5 expression was initially upregulated in response to T cell receptor stimulation, but diminished as the cells underwent proliferation, potentially explaining the differentiation-associated CD5 downregulation. Based on the proliferation-dependent downregulation of CD5, we hypothesized that relative CD5 expression could serve as a marker to distinguish the heterogeneous CD8+ T cell population based on their proliferation history. In support of this, we demonstrated that effector memory CD8+ T cells with higher CD5 expression exhibited phenotypic and functional characteristics resembling less differentiated cells compared to those with lower CD5 expression. Furthermore, in the retrospective analysis of PBMCs from 30 non-small cell lung cancer patients, we found that patients with higher CD5 expression in effector memory T cells displayed CD8+ T cells with a phenotype closer to the less differentiated cells, leading to favorable clinical outcomes in response to immune checkpoint inhibitor (ICI) therapy. These findings highlight the dynamics of CD5 expression as an indicator of CD8+ T cell differentiation status, and have implications for the development of predictive biomarker for ICI therapy.","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"23 4","pages":"e35"},"PeriodicalIF":6.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0a/71/in-23-e35.PMC10475823.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10171757","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}

引用次数: 0

IFN-γ: A Crucial Player in the Fight Against HBV Infection? IFN-γ:对抗HBV感染的关键角色?

IF 6 4区医学

Immune Network Pub Date : 2023-08-01 DOI: 10.4110/in.2023.23.e30

Marine Laure Bettina Hillaire, Philip Lawrence, Brice Lagrange

{"title":"IFN-γ: A Crucial Player in the Fight Against HBV Infection?","authors":"Marine Laure Bettina Hillaire, Philip Lawrence, Brice Lagrange","doi":"10.4110/in.2023.23.e30","DOIUrl":"https://doi.org/10.4110/in.2023.23.e30","url":null,"abstract":"About 0.8 million people die because of hepatitis B virus (HBV) infection each year. In around 5% of infected adults, the immune system is ineffective in countering HBV infection, leading to chronic hepatitis B (CHB). CHB is associated with hepatocellular carcinoma, which can lead to patient death. Unfortunately, although current treatments against CHB allow control of HBV infection, they are unable to achieve complete eradication of the virus. Cytokines of the IFN family represent part of the innate immune system and are key players in virus elimination. IFN secretion induces the expression of interferon stimulated genes, producing proteins that have antiviral properties and that are essential to cell-autonomous immunity. IFN-α is commonly used as a therapeutic approach for CHB. In addition, IFN-γ has been identified as the main IFN family member responsible for HBV eradication during acute infection. In this review, we summarize the key evidence gained from cellular or animal models of HBV replication or infection concerning the potential anti-HBV roles of IFN-γ with a particular focus on some IFN-γ-inducible genes.","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"23 4","pages":"e30"},"PeriodicalIF":6.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/10/8f/in-23-e30.PMC10475827.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10166477","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}

引用次数: 1

Tumor Promoting Function of DUSP10 in Non-Small Cell Lung Cancer Is Associated With Tumor-Promoting Cytokines. DUSP10在非小细胞肺癌中的促瘤功能与促瘤细胞因子相关

IF 6 4区医学

Immune Network Pub Date : 2023-08-01 DOI: 10.4110/in.2023.23.e34

Xing Wei, Chin Wen Png, Madhushanee Weerasooriya, Heng Li, Chenchen Zhu, Guiping Chen, Chuan Xu, Yongliang Zhang, Xiaohong Xu

{"title":"Tumor Promoting Function of DUSP10 in Non-Small Cell Lung Cancer Is Associated With Tumor-Promoting Cytokines.","authors":"Xing Wei, Chin Wen Png, Madhushanee Weerasooriya, Heng Li, Chenchen Zhu, Guiping Chen, Chuan Xu, Yongliang Zhang, Xiaohong Xu","doi":"10.4110/in.2023.23.e34","DOIUrl":"https://doi.org/10.4110/in.2023.23.e34","url":null,"abstract":"Lung cancer, particularly non-small cell lung cancer (NSCLC) which contributes more than 80% to totally lung cancer cases, remains the leading cause of cancer death and the 5-year survival is less than 20%. Continuous understanding on the mechanisms underlying the pathogenesis of this disease and identification of biomarkers for therapeutic application and response to treatment will help to improve patient survival. Here we found that a molecule known as DUSP10 (also known as MAPK phosphatase 5) is oncogenic in NSCLC. Overexpression of DUSP10 in NSCLC cells resulted in reduced activation of ERK and JNK, but increased activation of p38, which was associated with increased cellular growth and migration. When inoculated in immunodeficient mice, the DUSP10-overexpression NSCLC cells formed larger tumors compared to control cells. The increased growth of DUSP10-overexpression NSCLC cells was associated with increased expression of tumor-promoting cytokines including IL-6 and TGFβ. Importantly, higher DUSP10 expression was associated with poorer prognosis of NSCLC patients. Therefore, DUSP10 could severe as a biomarker for NSCLC prognosis and could be a target for development of therapeutic method for lung cancer treatment.","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"23 4","pages":"e34"},"PeriodicalIF":6.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5c/44/in-23-e34.PMC10475826.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10160202","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}

引用次数: 0

SARS-CoV-2 Infection Induces HMGB1 Secretion Through Post-Translational Modification and PANoptosis. SARS-CoV-2感染通过翻译后修饰和PANoptosis诱导HMGB1分泌

IF 6 4区医学

Immune Network Pub Date : 2023-06-01 DOI: 10.4110/in.2023.23.e26

Man Sup Kwak, Seoyeon Choi, Jiseon Kim, Hoojung Lee, In Ho Park, Jooyeon Oh, Duong Ngoc Mai, Nam-Hyuk Cho, Ki Taek Nam, Jeon-Soo Shin

{"title":"SARS-CoV-2 Infection Induces HMGB1 Secretion Through Post-Translational Modification and PANoptosis.","authors":"Man Sup Kwak, Seoyeon Choi, Jiseon Kim, Hoojung Lee, In Ho Park, Jooyeon Oh, Duong Ngoc Mai, Nam-Hyuk Cho, Ki Taek Nam, Jeon-Soo Shin","doi":"10.4110/in.2023.23.e26","DOIUrl":"https://doi.org/10.4110/in.2023.23.e26","url":null,"abstract":"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces excessive pro-inflammatory cytokine release and cell death, leading to organ damage and mortality. High-mobility group box 1 (HMGB1) is one of the damage-associated molecular patterns that can be secreted by pro-inflammatory stimuli, including viral infections, and its excessive secretion levels are related to a variety of inflammatory diseases. Here, the aim of the study was to show that SARS-CoV-2 infection induced HMGB1 secretion via active and passive release. Active HMGB1 secretion was mediated by post-translational modifications, such as acetylation, phosphorylation, and oxidation in HEK293E/ACE2-C-GFP and Calu-3 cells during SARS-CoV-2 infection. Passive release of HMGB1 has been linked to various types of cell death; however, we demonstrated for the first time that PANoptosis, which integrates other cell death pathways, including pyroptosis, apoptosis, and necroptosis, is related to passive HMGB1 release during SARS-CoV-2 infection. In addition, cytoplasmic translocation and extracellular secretion or release of HMGB1 were confirmed via immunohistochemistry and immunofluorescence in the lung tissues of humans and angiotensin-converting enzyme 2-overexpressing mice infected with SARS-CoV-2.","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"23 3","pages":"e26"},"PeriodicalIF":6.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/45/d2/in-23-e26.PMC10320423.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9806577","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}

引用次数: 4

NLRP3 Exacerbate NETosis-Associated Neuroinflammation in an LPS-Induced Inflamed Brain. NLRP3在脂多糖诱导的炎症脑中加剧nesis相关的神经炎症。

IF 6 4区医学

Immune Network Pub Date : 2023-06-01 DOI: 10.4110/in.2023.23.e27

Da Jeong Byun, Jaeho Lee, Je-Wook Yu, Young-Min Hyun

{"title":"NLRP3 Exacerbate NETosis-Associated Neuroinflammation in an LPS-Induced Inflamed Brain.","authors":"Da Jeong Byun, Jaeho Lee, Je-Wook Yu, Young-Min Hyun","doi":"10.4110/in.2023.23.e27","DOIUrl":"https://doi.org/10.4110/in.2023.23.e27","url":null,"abstract":"Neutrophil extracellular traps (NETs) exert a novel function of trapping pathogens. Released NETs can accumulate in inflamed tissues, be recognized by other immune cells for clearance, and lead to tissue toxicity. Therefore, the deleterious effect of NET is an etiological factor, causing several diseases directly or indirectly. NLR family pyrin domain containing 3 (NLRP3) in neutrophils is pivotal in signaling the innate immune response and is associated with several NET-related diseases. Despite these observations, the role of NLRP3 in NET formation in neuroinflammation remains elusive. Therefore, we aimed to explore NET formation promoted by NLRP3 in an LPS-induced inflamed brain. Wild-type and NLRP3 knockout mice were used to investigate the role of NLRP3 in NET formation. Brain inflammation was systemically induced by administering LPS. In such an environment, the NET formation was evaluated based on the expression of its characteristic indicators. DNA leakage and NET formation were analyzed in both mice through Western blot, flow cytometry, and in vitro live cell imaging as well as two-photon imaging. Our data revealed that NLRP3 promotes DNA leakage and facilitates NET formation accompanied by neutrophil death. Moreover, NLRP3 is not involved in neutrophil infiltration but is predisposed to boost NET formation, which is accompanied by neutrophil death in the LPS-induced inflamed brain. Furthermore, either NLRP3 deficiency or neutrophil depletion diminished pro-inflammatory cytokine, IL-1β, and alleviated blood-brain barrier damage. Overall, the results suggest that NLRP3 exacerbates NETosis in vitro and in the inflamed brain, aggravating neuroinflammation. These findings provide a clue that NLRP3 would be a potential therapeutic target to alleviate neuroinflammation.","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"23 3","pages":"e27"},"PeriodicalIF":6.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d4/a7/in-23-e27.PMC10320420.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10164631","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}

引用次数: 3