ImmunoHorizons最新文献_第10页

Lung Epithelial Regnase-1 Dampens Local Immune Response but Does Not Worsen Susceptibility to Klebsiella pneumoniae. 肺上皮调节酶-1会抑制局部免疫反应，但不会降低对肺炎克雷伯氏菌的易感性

ImmunoHorizons Pub Date : 2024-01-01 DOI: 10.4049/immunohorizons.2300082

Becky Lin, Li Fan, Shaterra Jackson, Aidan R Matunis, Dequan Lou, Kong Chen, Giraldina Trevejo-Nuñez

{"title":"Lung Epithelial Regnase-1 Dampens Local Immune Response but Does Not Worsen Susceptibility to Klebsiella pneumoniae.","authors":"Becky Lin, Li Fan, Shaterra Jackson, Aidan R Matunis, Dequan Lou, Kong Chen, Giraldina Trevejo-Nuñez","doi":"10.4049/immunohorizons.2300082","DOIUrl":"10.4049/immunohorizons.2300082","url":null,"abstract":"Klebsiella pneumoniae (KP) presents a global health threat, leading to significant morbidity and mortality due to its multidrug-resistant profile and the limited availability of therapeutic options. To eliminate KP lung infection, the host initiates a robust inflammatory response. One of the host's mechanisms for mitigating excessive inflammation involves the RNA-binding protein regnase-1 (Reg1, MCPIP1, or ZC3H12A). Reg1 has an RNA binding domain that recognizes stem-loop structures in the 3' untranslated region of various proinflammatory transcripts, leading to mRNA decay. However, excessive suppression of inflammation by Reg1 results in suboptimal KP control. Reg1 deficiency within the nonhematopoietic compartment confers resistance to KP in the lung. Given that lung epithelium is crucial for KP resistance, we hypothesized that selective deletion of Reg1 in lung epithelial cells might enhance proinflammatory signals, leading to a better control of KP. Our transcriptomic analysis of epithelial cells in KP-infected wild-type mice revealed the presence of three distinct alveolar type 2 cell (AT2) subpopulations (conventional, inflammatory, and cycling) and enrichment of Reg1 in inflammatory AT2 cells. We conditionally deleted Reg1 in lung AT2 cells (ΔReg1), which amplified the local inflammatory response in the lung and increased macrophage cell numbers compared with controls. However, when ΔReg1 mice were subjected to KP infection, there were no significant differences in bacterial burden or survival compared with controls. These findings suggest that the local inflammatory response enhanced by Reg1 deletion in AT2 cells is insufficient to control KP infection.","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"8 1","pages":"89-96"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10835647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139473043","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}

引用次数: 0

ImmunoHorizons Pub Date : 2024-01-01 DOI: 10.4049/immunohorizons.2300114

Svenja Meyhöfer, Armin Steffen, Kirstin Plötze-Martin, Jens-Uwe Marquardt, Sebastian M Meyhöfer, Karl-Ludwig Bruchhage, Ralph Pries

{"title":"Obesity-related Plasma CXCL10 Drives CX3CR1-dependent Monocytic Secretion of Macrophage Migration Inhibitory Factor.","authors":"Svenja Meyhöfer, Armin Steffen, Kirstin Plötze-Martin, Jens-Uwe Marquardt, Sebastian M Meyhöfer, Karl-Ludwig Bruchhage, Ralph Pries","doi":"10.4049/immunohorizons.2300114","DOIUrl":"10.4049/immunohorizons.2300114","url":null,"abstract":"Obesity is characterized by excessive body fat accumulation and comorbidities such as diabetes mellitus, cardiovascular disease, and obstructive sleep apnea syndrome (OSAS). Both obesity and OSAS are associated with immune disturbance, alterations of systemic inflammatory mediators, and immune cell recruitment to metabolic tissues. Chemokine CXCL10 is an important regulator of proinflammatory immune responses and is significantly increased in patients with severe obesity. This research project aims to investigate the impact of CXCL10 on human monocytes in patients with obesity. We studied the distribution of the CD14/CD16 monocyte subsets as well as their CX3CR1 expression patterns in whole-blood measurements from 92 patients with obesity and/or OSAS with regard to plasma CXCL10 values and individual clinical parameters. Furthermore, cytokine secretion by THP-1 monocytes in response to CXCL10 was analyzed. Data revealed significantly elevated plasma CXCL10 in patients with obesity with an additive effect of OSAS. CXCL10 was found to drive monocytic secretion of macrophage migration inhibitory factor via receptor protein CX3CR1, which significantly correlated with the individual body mass index. Our data show, for the first time, to our knowledge, that CX3CR1 is involved in alternative CXCL10 signaling in human monocytes in obesity-related inflammation. Obesity is a multifactorial disease, and further investigations regarding the complex interplay between obesity-related inflammatory mediators and systemic immune balances will help to better understand and improve the individual situation of our patients.","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"8 1","pages":"19-28"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10835669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139089746","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}

引用次数: 0

Gut Microbiota Is Associated with Onset and Severity of Type 1 Diabetes in Nonobese Diabetic Mice Treated with Anti-PD-1. 肠道微生物群与抗 PD-1 治疗的非肥胖糖尿病小鼠 1 型糖尿病的发病和严重程度有关。

ImmunoHorizons Pub Date : 2023-12-01 DOI: 10.4049/immunohorizons.2300103

Shriram Patel, Eugenia Becker, Corinne Ploix, Guido Steiner, Petar Scepanovic, Matthias Fueth, Maria Cristina de Vera Mudry, Anne Eichinger-Chapelon, Estelle Marrer-Berger, Marcus J Claesson

{"title":"Gut Microbiota Is Associated with Onset and Severity of Type 1 Diabetes in Nonobese Diabetic Mice Treated with Anti-PD-1.","authors":"Shriram Patel, Eugenia Becker, Corinne Ploix, Guido Steiner, Petar Scepanovic, Matthias Fueth, Maria Cristina de Vera Mudry, Anne Eichinger-Chapelon, Estelle Marrer-Berger, Marcus J Claesson","doi":"10.4049/immunohorizons.2300103","DOIUrl":"10.4049/immunohorizons.2300103","url":null,"abstract":"Our bodies are home to individual-specific microbial ecosystems that have recently been found to be modified by cancer immunotherapies. The interaction between the gut microbiome and islet autoimmunity leading to type I diabetes (T1D) is well described and highlights the microbiome contribution during the onset and T1D development in animals and humans. As cancer immunotherapies induce gut microbiome perturbations and immune-mediated adverse events in susceptible patients, we hypothesized that NOD mice can be used as a predictive tool to investigate the effects of anti-PD-1 treatment on the onset and severity of T1D, and how microbiota influences immunopathology. In this longitudinal study, we showed that anti-PD-1 accelerated T1D onset, increased glutamic acid decarboxylase-reactive T cell frequency in spleen, and precipitated destruction of β cells, triggering high glucose levels and pancreatic islet reduction. Anti-PD-1 treatment also resulted in temporal microbiota changes and lower diversity characteristic of T1D. Finally, we identified known insulin-resistance regulating bacteria that were negatively correlated with glucose levels, indicating that anti-PD-1 treatment impacts the early gut microbiota composition. Moreover, an increase of mucin-degrading Akkermansia muciniphila points to alterations of barrier function and immune system activation. These results highlight the ability of microbiota to readily respond to therapy-triggered pathophysiological changes as rescuers (Bacteroides acidifaciens and Parabacteroides goldsteinii) or potential exacerbators (A. muciniphila). Microbiome-modulating interventions may thus be promising mitigation strategies for immunotherapies with high risk of immune-mediated adverse events.","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"7 12","pages":"872-885"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10759162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139038347","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}

引用次数: 0

Side-by-Side Comparison of Compensation Beads Used in Polychromatic Flow Cytometry. 多色流式细胞术中补偿珠的并排比较。

ImmunoHorizons Pub Date : 2023-12-01 DOI: 10.4049/immunohorizons.2300066

Debajit Bhowmick, Sara K Lowe, Michelle L Ratliff

引用次数: 0

No Evidence That Analgesic Use after COVID-19 Vaccination Negatively Impacts Antibody Responses. 没有证据表明接种 COVID-19 疫苗后使用镇痛剂会对抗体反应产生负面影响。

ImmunoHorizons Pub Date : 2023-12-01 DOI: 10.4049/immunohorizons.2300090

Bonnie J Lafleur, Lisa White, Michael D Dake, Janko Z Nikolich, Ryan Sprissler, Deepta Bhattacharya

{"title":"No Evidence That Analgesic Use after COVID-19 Vaccination Negatively Impacts Antibody Responses.","authors":"Bonnie J Lafleur, Lisa White, Michael D Dake, Janko Z Nikolich, Ryan Sprissler, Deepta Bhattacharya","doi":"10.4049/immunohorizons.2300090","DOIUrl":"10.4049/immunohorizons.2300090","url":null,"abstract":"Uptake of mRNA vaccines, especially booster immunizations, against COVID-19 has been lower than hoped, perhaps in part due to their reactogenicity. Analgesics might alleviate symptoms associated with vaccination, but they might also impact immune responses. We semiquantitatively measured Ab responses following COVID-19 vaccination in 2354 human participants surveyed about analgesic use after vaccination. Participants who used nonsteroidal anti-inflammatory drugs or acetaminophen after vaccination showed elevated Ab levels against the receptor-binding domain of Spike protein relative to those who did not use analgesics. This pattern was observed for both mRNA-1273 and BNT162b2 and across age groups. Participants who used analgesics more frequently reported fatigue, muscle aches, and headaches than did those who did not use painkillers. Among participants who reported these symptoms, we observed no statistically significant differences in Ab levels irrespective of analgesic use. These data suggest that elevated Ab levels are associated with symptoms and inflammatory processes rather than painkiller use per se. Taken together, we find no evidence that analgesic use reduces Ab responses after COVID-19 vaccination. Recommendation of their use to alleviate symptoms might improve uptake of booster immunizations.","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"7 12","pages":"834-841"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10759157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138815116","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}

引用次数: 0

Bovine Serum Albumin Elicits IL-33-Dependent Adipose Tissue Eosinophilia: Potential Relevance to Ovalbumin-induced Models of Allergic Disease. 牛血清白蛋白诱发 IL-33 依赖性脂肪组织嗜酸性粒细胞增多：与卵清蛋白诱导的过敏性疾病模型的潜在相关性。

ImmunoHorizons Pub Date : 2023-12-01 DOI: 10.4049/immunohorizons.2300061

Heather L Caslin, W Reid Bolus, Christopher Thomas, Shinji Toki, Allison E Norlander, R Stokes Peebles, Alyssa H Hasty

{"title":"Bovine Serum Albumin Elicits IL-33-Dependent Adipose Tissue Eosinophilia: Potential Relevance to Ovalbumin-induced Models of Allergic Disease.","authors":"Heather L Caslin, W Reid Bolus, Christopher Thomas, Shinji Toki, Allison E Norlander, R Stokes Peebles, Alyssa H Hasty","doi":"10.4049/immunohorizons.2300061","DOIUrl":"10.4049/immunohorizons.2300061","url":null,"abstract":"All cells of the immune system reside in adipose tissue (AT), and increasing type 2 immune cells may be a therapeutic strategy to improve metabolic health. In our previous study using i.p. IL-5 injections to increase eosinophils, we observed that a standard vehicle control of 0.1% BSA also elicited profound AT eosinophilia. In this study, we aimed to determine whether BSA-induced AT eosinophilia results in metabolic benefits in murine models of diet-induced obesity. I.p. 0.1% BSA injections increased AT eosinophils after 4 wk. Despite elevating eosinophils to >50% of immune cells in the AT, body weight and glucose tolerance were not different between groups. Interestingly, BSA elicited epithelial IL-33 production, as well as gene expression for type 2 cytokines and IgE production that were dependent on IL-33. Moreover, multiple models of OVA sensitization also drove AT eosinophilia. Following transplantation of a donor fat pad with BSA-induced eosinophilia, OVA-sensitized recipient mice had higher numbers of bronchoalveolar lavage eosinophils that were recipient derived. Interestingly, lungs of recipient mice contained eosinophils, macrophages, and CD8 T cells from the donor AT. These trafficked similarly from BSA- and non-BSA-treated AT, suggesting even otherwise healthy AT serves as a reservoir of immune cells capable of migrating to the lungs. In conclusion, our studies suggest that i.p. injections of BSA and OVA induce an allergic response in the AT that elicits eosinophil recruitment, which may be an important consideration for those using OVA in animal models of allergic disease.","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"7 12","pages":"842-852"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10759155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138815108","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}

引用次数: 0

Recent Advances in the Development of Monoclonal Antibodies and Next-Generation Antibodies. 单克隆抗体和新一代抗体开发的最新进展。

ImmunoHorizons Pub Date : 2023-12-01 DOI: 10.4049/immunohorizons.2300102

Rohit Singh, Pankaj Chandley, Soma Rohatgi

{"title":"Recent Advances in the Development of Monoclonal Antibodies and Next-Generation Antibodies.","authors":"Rohit Singh, Pankaj Chandley, Soma Rohatgi","doi":"10.4049/immunohorizons.2300102","DOIUrl":"10.4049/immunohorizons.2300102","url":null,"abstract":"mAbs are highly indispensable tools for diagnostic, prophylactic, and therapeutic applications. The first technique, hybridoma technology, was based on fusion of B lymphocytes with myeloma cells, which resulted in generation of single mAbs against a specific Ag. Along with hybridoma technology, several novel and alternative methods have been developed to improve mAb generation, ranging from electrofusion to the discovery of completely novel technologies such as B cell immortalization; phage, yeast, bacterial, ribosome, and mammalian display systems; DNA/RNA encoded Abs; single B cell technology; transgenic animals; and artificial intelligence/machine learning. This commentary outlines the evolution, methodology, advantages, and limitations of various mAb production techniques. Furthermore, with the advent of next-generation Ab technologies such as single-chain variable fragments, nanobodies, bispecific Abs, Fc-engineered Abs, Ab biosimilars, Ab mimetics, and Ab-drug conjugates, the healthcare and pharmaceutical sectors have become resourceful to develop highly specific mAb treatments against various diseases such as cancer and autoimmune and infectious diseases.","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"7 12","pages":"886-897"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10759153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139041137","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}

引用次数: 0

Intravascular Leukocyte Labeling Refines the Distribution of Myeloid Cells in the Lung in Models of Allergen-induced Airway Inflammation. 血管内白细胞标记细化了过敏原诱发气道炎症模型中肺部髓系细胞的分布。

ImmunoHorizons Pub Date : 2023-12-01 DOI: 10.4049/immunohorizons.2300059

Yu-Hua Chow, Ryan C Murphy, Dowon An, Ying Lai, William A Altemeier, Anne M Manicone, Teal S Hallstrand

{"title":"Intravascular Leukocyte Labeling Refines the Distribution of Myeloid Cells in the Lung in Models of Allergen-induced Airway Inflammation.","authors":"Yu-Hua Chow, Ryan C Murphy, Dowon An, Ying Lai, William A Altemeier, Anne M Manicone, Teal S Hallstrand","doi":"10.4049/immunohorizons.2300059","DOIUrl":"10.4049/immunohorizons.2300059","url":null,"abstract":"Innate immune cell populations are critical in asthma with different functional characteristics based on tissue location, which has amplified the importance of characterizing the precise number and location of innate immune populations in murine models of asthma. In this study, we performed premortem intravascular (IV) labeling of leukocytes in mice in two models of asthma to differentiate innate immune cell populations within the IV compartment versus those residing in the lung tissue or airway lumen. We performed spectral flow cytometry analysis of the blood, suspensions of digested lung tissue, and bronchoalveolar lavage fluid. We discovered that IV labeled leukocytes do not contaminate analysis of bronchoalveolar lavage fluid but represent a significant proportion of cells in digested lung tissue. Exclusion of IV leukocytes significantly improved the accuracy of the assessments of myeloid cells in the lung tissue and provided important insights into ongoing trafficking in both eosinophilic and neutrophilic asthma models.","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"7 12","pages":"853-860"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10759158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138815111","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}

引用次数: 0

Sodium-Glucose Cotransporter-2 Inhibitor, Empagliflozin, Suppresses the Inflammatory Immune Response to Influenza Infection. 葡萄糖钠转运体 2 抑制剂 Empagliflozin 可抑制流感感染的炎症免疫反应

ImmunoHorizons Pub Date : 2023-12-01 DOI: 10.4049/immunohorizons.2300077

Nicholas J Constantinesco, Baskaran Chinnappan, Louis J DeVito, Crystal Moras, Sashwath Srikanth, Maria de la Luz Garcia-Hernandez, Javier Rangel-Moreno, Radha Gopal

{"title":"Sodium-Glucose Cotransporter-2 Inhibitor, Empagliflozin, Suppresses the Inflammatory Immune Response to Influenza Infection.","authors":"Nicholas J Constantinesco, Baskaran Chinnappan, Louis J DeVito, Crystal Moras, Sashwath Srikanth, Maria de la Luz Garcia-Hernandez, Javier Rangel-Moreno, Radha Gopal","doi":"10.4049/immunohorizons.2300077","DOIUrl":"10.4049/immunohorizons.2300077","url":null,"abstract":"Influenza is a highly contagious, acute respiratory disease that causes significant public health and economic threats. Influenza infection induces various inflammatory mediators, IFNs, and recruitment of inflammatory cells in the host. This inflammatory \"cytokine storm\" is thought to play a role in influenza-induced lung pathogenesis. Empagliflozin is a drug primarily used to lower blood glucose in type II diabetes patients by inhibiting the sodium-glucose cotransporter-2 (SGLT-2) found in the proximal tubules in the kidneys. In this study, we have investigated the effects of empagliflozin on the pulmonary immune response to influenza infection. C57BL/6 mice (wild type) were infected with influenza A/PR/8/34 and treated with empagliflozin, and the disease outcomes were analyzed. Empagliflozin treatment decreased the expression of the inflammatory cytokines IL-1β, IL-6, and CCL2; the percentage of inflammatory monocytes and inducible NO synthase-positive macrophages; and IFN response genes Stat1 and CXCL9 during influenza infection. Further, empagliflozin treatment decreases the expression of IL-6, CCL2, and CCL5 in RAW264.7 macrophages and bone marrow-derived macrophages. However, empagliflozin treatment increased influenza viral titer during infection. Despite fostering an increased viral burden, treatment with empagliflozin decreases the mortality in wild type and high fat diet-induced atherosclerotic LDLR-/- mice. Based on our findings, empagliflozin may have therapeutic implications for use in patients to prevent lung damage and acute respiratory illness.","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"7 12","pages":"861-871"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10759161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138815121","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}

引用次数: 0

Egr2 Deletion in Autoimmune-Prone C57BL6/lpr Mice Suppresses the Expression of Methylation-Sensitive Dlk1-Dio3 Cluster MicroRNAs. 自身免疫易感性 C57BL6/lpr 小鼠的 Egr2 基因缺失抑制甲基化敏感的 Dlk1-Dio3 簇 MicroRNAs 的表达

ImmunoHorizons Pub Date : 2023-12-01 DOI: 10.4049/immunohorizons.2300111

Zhuang Wang, Bettina Heid, Jianlin He, Hehuang Xie, Christopher M Reilly, Rujuan Dai, S Ansar Ahmed

{"title":"Egr2 Deletion in Autoimmune-Prone C57BL6/lpr Mice Suppresses the Expression of Methylation-Sensitive Dlk1-Dio3 Cluster MicroRNAs.","authors":"Zhuang Wang, Bettina Heid, Jianlin He, Hehuang Xie, Christopher M Reilly, Rujuan Dai, S Ansar Ahmed","doi":"10.4049/immunohorizons.2300111","DOIUrl":"10.4049/immunohorizons.2300111","url":null,"abstract":"We previously demonstrated that the upregulation of microRNAs (miRNAs) at the genomic imprinted Dlk1-Dio3 locus in murine lupus is correlated with global DNA hypomethylation. We now report that the Dlk1-Dio3 genomic region in CD4+ T cells of MRL/lpr mice is hypomethylated, linking it to increased Dlk1-Dio3 miRNA expression. We evaluated the gene expression of methylating enzymes, DNA methyltransferases (DNMTs), and demethylating ten-eleven translocation proteins (TETs) to elucidate the molecular basis of DNA hypomethylation in lupus CD4+ T cells. There was a significantly elevated expression of Dnmt1 and Dnmt3b, as well as Tet1 and Tet2, in CD4+ T cells of three different lupus-prone mouse strains compared to controls. These findings suggest that the hypomethylation of murine lupus CD4+ T cells is likely attributed to a TET-mediated active demethylation pathway. Moreover, we found that deletion of early growth response 2 (Egr2), a transcription factor gene in B6/lpr mice markedly reduced maternally expressed miRNA genes but not paternally expressed protein-coding genes at the Dlk1-Dio3 locus in CD4+ T cells. EGR2 has been shown to induce DNA demethylation by recruiting TETs. Surprisingly, we found that deleting Egr2 in B6/lpr mice induced more hypomethylated differentially methylated regions at either the whole-genome level or the Dlk1-Dio3 locus in CD4+ T cells. Although the role of methylation in EGR2-mediated regulation of Dlk1-Dio3 miRNAs is not readily apparent, these are the first data to show that in lupus, Egr2 regulates Dlk1-Dio3 miRNAs, which target major signaling pathways in autoimmunity. These data provide a new perspective on the role of upregulated EGR2 in lupus pathogenesis.","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"7 12","pages":"898-907"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10759154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139050008","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}

引用次数: 0