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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,&nbsp;Sang-Hoon Kim,&nbsp;Mi Seon Han,&nbsp;Yoonsun Yoon,&nbsp;Yun-Kyung Kim,&nbsp;Hye-Kyung Cho,&nbsp;Ki Wook Yun,&nbsp;Seung Ha Song,&nbsp;Bin Ahn,&nbsp;Ye Kyung Kim,&nbsp;Sung Hwan Choi,&nbsp;Young June Choe,&nbsp;Heeji Lim,&nbsp;Eun Bee Choi,&nbsp;Kwangwook Kim,&nbsp;Seokhwan Hyeon,&nbsp;Hye Jung Lim,&nbsp;Byung-Chul Kim,&nbsp;Yoo-Kyoung Lee,&nbsp;Eun Hwa Choi,&nbsp;Eui-Cheol Shin,&nbsp;Hyunju Lee","doi":"10.4110/in.2023.23.e33","DOIUrl":"https://doi.org/10.4110/in.2023.23.e33","url":null,"abstract":"<p><p>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<sup>+</sup> T cells exhibited substantial responses against both ancestral and Omicron spike proteins. Notably, CD4<sup>+</sup> 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.</p>","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,&nbsp;Kyu Seong Park,&nbsp;Gwang Bin Lee,&nbsp;Sang-Eun Park,&nbsp;Jae-Hoon Choi,&nbsp;Myeong Hee Moon","doi":"10.4110/in.2023.23.e28","DOIUrl":"https://doi.org/10.4110/in.2023.23.e28","url":null,"abstract":"<p><p>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 <i>Ldlr</i><sup>-/-</sup> 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 <i>Pnpla2</i> and <i>Lpl</i> were markedly increased but expressions of <i>Lpin2</i> and <i>Dgat1</i> 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.</p>","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<sup>+</sup> T Cells Predicting Clinical Response to Immunotherapy.","authors":"Young Ju Kim,&nbsp;Kyung Na Rho,&nbsp;Saei Jeong,&nbsp;Gil-Woo Lee,&nbsp;Hee-Ok Kim,&nbsp;Hyun-Ju Cho,&nbsp;Woo Kyun Bae,&nbsp;In-Jae Oh,&nbsp;Sung-Woo Lee,&nbsp;Jae-Ho Cho","doi":"10.4110/in.2023.23.e35","DOIUrl":"https://doi.org/10.4110/in.2023.23.e35","url":null,"abstract":"<p><p>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<sup>+</sup> 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<sup>+</sup> 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<sup>+</sup> T cell population based on their proliferation history. In support of this, we demonstrated that effector memory CD8<sup>+</sup> 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<sup>+</sup> 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<sup>+</sup> T cell differentiation status, and have implications for the development of predictive biomarker for ICI therapy.</p>","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,&nbsp;Philip Lawrence,&nbsp;Brice Lagrange","doi":"10.4110/in.2023.23.e30","DOIUrl":"https://doi.org/10.4110/in.2023.23.e30","url":null,"abstract":"<p><p>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.</p>","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,&nbsp;Chin Wen Png,&nbsp;Madhushanee Weerasooriya,&nbsp;Heng Li,&nbsp;Chenchen Zhu,&nbsp;Guiping Chen,&nbsp;Chuan Xu,&nbsp;Yongliang Zhang,&nbsp;Xiaohong Xu","doi":"10.4110/in.2023.23.e34","DOIUrl":"https://doi.org/10.4110/in.2023.23.e34","url":null,"abstract":"<p><p>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.</p>","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,&nbsp;Seoyeon Choi,&nbsp;Jiseon Kim,&nbsp;Hoojung Lee,&nbsp;In Ho Park,&nbsp;Jooyeon Oh,&nbsp;Duong Ngoc Mai,&nbsp;Nam-Hyuk Cho,&nbsp;Ki Taek Nam,&nbsp;Jeon-Soo Shin","doi":"10.4110/in.2023.23.e26","DOIUrl":"https://doi.org/10.4110/in.2023.23.e26","url":null,"abstract":"<p><p>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.</p>","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,&nbsp;Jaeho Lee,&nbsp;Je-Wook Yu,&nbsp;Young-Min Hyun","doi":"10.4110/in.2023.23.e27","DOIUrl":"https://doi.org/10.4110/in.2023.23.e27","url":null,"abstract":"<p><p>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 <i>in vitro</i> 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 <i>in vitro</i> and in the inflamed brain, aggravating neuroinflammation. These findings provide a clue that NLRP3 would be a potential therapeutic target to alleviate neuroinflammation.</p>","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
Altered Frequency, Activation, and Clinical Relevance of Circulating Innate and Innate-Like Lymphocytes in Patients With Alcoholic Liver Cirrhosis. 酒精性肝硬化患者循环先天和先天样淋巴细胞的频率、激活和临床相关性
IF 6 4区 医学
Immune Network Pub Date : 2023-06-01 DOI: 10.4110/in.2023.23.e22
Ki-Jeong Park, Hye-Mi Jin, Young-Nan Cho, Jae Hyun Yoon, Seung-Jung Kee, Hyo-Sin Kim, Yong-Wook Park
{"title":"Altered Frequency, Activation, and Clinical Relevance of Circulating Innate and Innate-Like Lymphocytes in Patients With Alcoholic Liver Cirrhosis.","authors":"Ki-Jeong Park,&nbsp;Hye-Mi Jin,&nbsp;Young-Nan Cho,&nbsp;Jae Hyun Yoon,&nbsp;Seung-Jung Kee,&nbsp;Hyo-Sin Kim,&nbsp;Yong-Wook Park","doi":"10.4110/in.2023.23.e22","DOIUrl":"https://doi.org/10.4110/in.2023.23.e22","url":null,"abstract":"<p><p>Alcoholic liver cirrhosis (ALC) is caused by chronic alcohol overconsumption and might be linked to dysregulated immune responses in the gut-liver axis. However, there is a lack of comprehensive research on levels and functions of innate lymphocytes including mucosal-associated invariant T (MAIT) cells, NKT cells, and NK (NK) cells in ALC patients. Thus, the aim of this study was to examine the levels and function of these cells, evaluate their clinical relevance, and explore their immunologic roles in the pathogenesis of ALC. Peripheral blood samples from ALC patients (n = 31) and healthy controls (HCs, n = 31) were collected. MAIT cells, NKT cells, NK cells, cytokines, CD69, PD-1, and lymphocyte-activation gene 3 (LAG-3) levels were measured by flow cytometry. Percentages and numbers of circulating MAIT cells, NKT cells, and NK cells were significantly reduced in ALC patients than in HCs. MAIT cell exhibited increased production of IL-17 and expression levels of CD69, PD-1, and LAG-3. NKT cells displayed decreased production of IFN-γ and IL-4. NK cells showed elevated CD69 expression. Absolute MAIT cell levels were positively correlated with lymphocyte count but negatively correlated with C-reactive protein. In addition, NKT cell levels were negatively correlated with hemoglobin levels. Furthermore, log-transformed absolute MAIT cell levels were negatively correlated with the Age, Bilirubin, INR, and Creatinine score. This study demonstrates that circulating MAIT cells, NKT cells, and NK cells are numerically deficient in ALC patients, and the degree of cytokine production and activation status also changed. Besides, some of their deficiencies are related to several clinical parameters. These findings provide important information about immune responses of ALC patients.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"23 3","pages":"e22"},"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/5b/e7/in-23-e22.PMC10320422.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10183567","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
Extracellular Acidification Augments NLRP3-Mediated Inflammasome Signaling in Macrophages. 细胞外酸化增强巨噬细胞nlrp3介导的炎性小体信号传导。
IF 6 4区 医学
Immune Network Pub Date : 2023-06-01 DOI: 10.4110/in.2023.23.e23
Byeong Jun Chae, Kyung-Seo Lee, Inhwa Hwang, Je-Wook Yu
{"title":"Extracellular Acidification Augments NLRP3-Mediated Inflammasome Signaling in Macrophages.","authors":"Byeong Jun Chae,&nbsp;Kyung-Seo Lee,&nbsp;Inhwa Hwang,&nbsp;Je-Wook Yu","doi":"10.4110/in.2023.23.e23","DOIUrl":"https://doi.org/10.4110/in.2023.23.e23","url":null,"abstract":"<p><p>Inflammation is a series of host defense processes in response to microbial infection and tissue injury. Inflammatory processes frequently cause extracellular acidification in the inflamed region through increased glycolysis and lactate secretion. Therefore, the immune cells infiltrating the inflamed region encounter an acidic microenvironment. Extracellular acidosis can modulate the innate immune response of macrophages; however, its role for inflammasome signaling still remains elusive. In the present study, we demonstrated that macrophages exposed to an acidic microenvironment exhibited enhanced caspase-1 processing and IL-1β secretion compared with those under physiological pH. Moreover, exposure to an acidic pH increased the ability of macrophages to assemble the NLR family pyrin domain containing 3 (NLRP3) inflammasome in response to an NLRP3 agonist. This acidosis-mediated augmentation of NLRP3 inflammasome activation occurred in bone marrow-derived macrophages but not in bone marrow-derived neutrophils. Notably, exposure to an acidic environment caused a reduction in the intracellular pH of macrophages but not neutrophils. Concordantly, macrophages, but not neutrophils, exhibited NLRP3 agonist-mediated translocation of chloride intracellular channel protein 1 (CLIC1) into their plasma membranes under an acidic microenvironment. Collectively, our results demonstrate that extracellular acidosis during inflammation can increase the sensitivity of NLRP3 inflammasome formation and activation in a CLIC1-dependent manner. Thus, CLIC1 may be a potential therapeutic target for NLRP3 inflammasome-mediated pathological conditions.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"23 3","pages":"e23"},"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/34/87/in-23-e23.PMC10320421.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10183570","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
The Immunosuppressive Potential of Cholesterol Sulfate Through T Cell Microvilli Disruption. 硫酸胆固醇通过破坏T细胞微绒毛的免疫抑制潜能。
IF 6 4区 医学
Immune Network Pub Date : 2023-06-01 DOI: 10.4110/in.2023.23.e29
Jeong-Su Park, Ik-Joo Chung, Hye-Ran Kim, Chang-Duk Jun
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