Pub Date : 2024-11-22DOI: 10.1016/j.molimm.2024.11.008
Yatian Yang , Rui Wu , Chengcheng Qian , Deling Wu , Jinmei Ou
The gut microbiota plays a crucial role in the development of colitis by influencing the immune response and inflammation in the colon. Previous research has shown that Mume Fructus, a traditional Chinese medicine, can alleviate colitis by reducing the activity of inflammatory pathways. However, the specific connection between Mume Fructus-treated colitis and regulation of gut flora remains unclear, prompting further investigation. This research aims to delve deeper into the possible impact of the gut microbiota in colitis when treated with the aqueous decoction of Mume Fructus (MF). The effects of MF on rats with DSS-induced colitis were assessed through examination of pathological indicators, intestinal barrier proteins, and analysis of 16S rDNA sequencing to investigate its impact on the gut microbiota. In addition, the colon contents of rats after the administration of MF were transplanted into rats with colitis, and the effect of MF on intestinal flora was verified, and “beneficial bacteria” were identified by 16S rDNA sequencing and Spearman’s correlation analysis. In summary, our findings suggest that MF has the potential to ameliorate symptoms of colitis through modulation of intestinal microbiota and restoration of intestinal barrier function.
{"title":"Mume fructus alters the abundance of intestinal microbiota and alleviates damaged intestinal barrier and inflammation in rats with DSS induced colitis","authors":"Yatian Yang , Rui Wu , Chengcheng Qian , Deling Wu , Jinmei Ou","doi":"10.1016/j.molimm.2024.11.008","DOIUrl":"10.1016/j.molimm.2024.11.008","url":null,"abstract":"<div><div>The gut microbiota plays a crucial role in the development of colitis by influencing the immune response and inflammation in the colon. Previous research has shown that Mume Fructus, a traditional Chinese medicine, can alleviate colitis by reducing the activity of inflammatory pathways. However, the specific connection between Mume Fructus-treated colitis and regulation of gut flora remains unclear, prompting further investigation. This research aims to delve deeper into the possible impact of the gut microbiota in colitis when treated with the aqueous decoction of Mume Fructus (MF). The effects of MF on rats with DSS-induced colitis were assessed through examination of pathological indicators, intestinal barrier proteins, and analysis of 16S rDNA sequencing to investigate its impact on the gut microbiota. In addition, the colon contents of rats after the administration of MF were transplanted into rats with colitis, and the effect of MF on intestinal flora was verified, and “beneficial bacteria” were identified by 16S rDNA sequencing and Spearman’s correlation analysis. In summary, our findings suggest that MF has the potential to ameliorate symptoms of colitis through modulation of intestinal microbiota and restoration of intestinal barrier function.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"176 ","pages":"Pages 60-72"},"PeriodicalIF":3.2,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-21DOI: 10.1016/j.molimm.2024.11.007
Zhenhao Shao , Xu Ding , Yiting Zhou , Jiabin Zhou , Yu Luo , Dan Wu , Yufei Dai , Lingling Qian , Ruxing Wang , Zhiming Yu
In the context of liver cirrhosis, the incidence of myocardial inflammation and apoptosis escalates, contributing to the development and progression of cirrhotic cardiomyopathy. The P2X7 receptor, a purinergic receptor linked to inflammatory processes, has been identified in the etiology of a range of autoinflammatory, autoimmune, chronic inflammatory, and metabolic disorders. Despite this, the specific role of the P2X7 receptor in the etiology of cirrhotic cardiomyopathy remains to be elucidated. In our research, a cirrhotic cardiomyopathy animal model was established using mice subjected to bile duct ligation. The expression of the P2X7 receptor was suppressed via intraperitoneal administration of Brilliant Blue G. Cardiac function was evaluated using echocardiographic techniques, while histopathological examination and enzyme-linked immunosorbent assays were employed to assess the presence of inflammation and apoptosis in liver and cardiac tissues. The expression of key proteins, including P2X7, NLRP3, and IL-1β, in the myocardial tissue was quantified by Western blot analysis. Our research has unveiled significant findings in a murine model of liver fibrosis induced by two weeks of bile duct ligation. Notably, we detected escalated levels of liver fibrosis coupled with disruptions in liver blood flow dynamics. Concurrently, there was a marked increase in myocardial inflammation and apoptosis, which adversely affected heart function. Intriguingly, the expression of P2X7 receptors (P2X7R) in cardiac and hepatic tissues was found to be significantly elevated. Targeting and inhibiting the expression of P2X7R not only alleviated myocardial inflammation and apoptosis but also enhanced cardiac performance. Furthermore, this intervention resulted in a noticeable reduction in liver fibrosis. The interplay between the P2X7 and NLRP3 pathways emerges as a pivotal mechanism in the etiology and progression of cirrhotic cardiomyopathy. Our findings suggest that modulating the P2X7-NLRP3 axis could offer promising therapeutic avenues for managing cirrhotic cardiomyopathy.
在肝硬化的情况下，心肌炎症和细胞凋亡的发生率会增加，从而导致肝硬化性心肌病的发生和发展。P2X7 受体是一种与炎症过程有关的嘌呤能受体，已被确认与一系列自身炎症、自身免疫、慢性炎症和代谢性疾病的病因有关。尽管如此，P2X7 受体在肝硬化心肌病病因中的具体作用仍有待阐明。在我们的研究中，利用胆管结扎小鼠建立了肝硬化心肌病动物模型。通过腹腔注射亮蓝 G 抑制 P2X7 受体的表达，使用超声心动图技术评估心脏功能，并使用组织病理学检查和酶联免疫吸附试验评估肝脏和心脏组织中是否存在炎症和细胞凋亡。通过 Western 印迹分析，对心肌组织中 P2X7、NLRP3 和 IL-1β 等关键蛋白的表达进行了量化。我们的研究在为期两周的胆管结扎诱导的鼠肝纤维化模型中取得了重大发现。值得注意的是，我们发现肝脏纤维化程度加剧，同时肝脏血流动力学发生紊乱。与此同时，心肌炎症和细胞凋亡明显增加，对心脏功能产生了不利影响。耐人寻味的是，在心脏和肝组织中发现 P2X7 受体（P2X7R）的表达明显升高。靶向抑制 P2X7R 的表达不仅能缓解心肌炎症和细胞凋亡，还能增强心脏功能。此外，这种干预还能明显减轻肝纤维化。P2X7 和 NLRP3 通路之间的相互作用成为肝硬化心肌病病因和进展的关键机制。我们的研究结果表明，调节P2X7-NLRP3轴可为控制肝硬化心肌病提供有前景的治疗途径。
{"title":"The role and mechanism of P2X7R in cirrhotic cardiomyopathy","authors":"Zhenhao Shao , Xu Ding , Yiting Zhou , Jiabin Zhou , Yu Luo , Dan Wu , Yufei Dai , Lingling Qian , Ruxing Wang , Zhiming Yu","doi":"10.1016/j.molimm.2024.11.007","DOIUrl":"10.1016/j.molimm.2024.11.007","url":null,"abstract":"<div><div>In the context of liver cirrhosis, the incidence of myocardial inflammation and apoptosis escalates, contributing to the development and progression of cirrhotic cardiomyopathy. The P2X7 receptor, a purinergic receptor linked to inflammatory processes, has been identified in the etiology of a range of autoinflammatory, autoimmune, chronic inflammatory, and metabolic disorders. Despite this, the specific role of the P2X7 receptor in the etiology of cirrhotic cardiomyopathy remains to be elucidated. In our research, a cirrhotic cardiomyopathy animal model was established using mice subjected to bile duct ligation. The expression of the P2X7 receptor was suppressed via intraperitoneal administration of Brilliant Blue G. Cardiac function was evaluated using echocardiographic techniques, while histopathological examination and enzyme-linked immunosorbent assays were employed to assess the presence of inflammation and apoptosis in liver and cardiac tissues. The expression of key proteins, including P2X7, NLRP3, and IL-1β, in the myocardial tissue was quantified by Western blot analysis. Our research has unveiled significant findings in a murine model of liver fibrosis induced by two weeks of bile duct ligation. Notably, we detected escalated levels of liver fibrosis coupled with disruptions in liver blood flow dynamics. Concurrently, there was a marked increase in myocardial inflammation and apoptosis, which adversely affected heart function. Intriguingly, the expression of P2X7 receptors (P2X7R) in cardiac and hepatic tissues was found to be significantly elevated. Targeting and inhibiting the expression of P2X7R not only alleviated myocardial inflammation and apoptosis but also enhanced cardiac performance. Furthermore, this intervention resulted in a noticeable reduction in liver fibrosis. The interplay between the P2X7 and NLRP3 pathways emerges as a pivotal mechanism in the etiology and progression of cirrhotic cardiomyopathy. Our findings suggest that modulating the P2X7-NLRP3 axis could offer promising therapeutic avenues for managing cirrhotic cardiomyopathy.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"176 ","pages":"Pages 49-59"},"PeriodicalIF":3.2,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-19DOI: 10.1016/j.molimm.2024.11.005
A.L. Alexander , E.K. Doyle , P. Alexandre , B.C. Hine , T. Vuocolo , N.M. Andronicos , A. Reverter , I.G. Colditz , A.B. Ingham
Background
Innate immune stimulants, including mycobacterium cell wall fractions (MCWF), offer an alternative control option to prevent and treat disease in livestock, by appropriately augmenting the innate immune response. However, the functional response to mycobacterium cell wall fractions in cattle is not well defined. In this study we report the transcriptomic response of bovine peripheral blood mononuclear cells to MCWF in the product Amplimune®.
Methods
Amplimune-induced transcriptomic changes in bovine peripheral blood mononuclear cells were determined following an initial pilot study and a later time course experiment. These cells were cultured in vitro for 24 h. In the pilot experiment, cells were stimulated with 0, 2, 5, 12.5 or 31.25 µg/mL Amplimune. In the time course experiment, cells were stimulated with 0 or 31.25 µg/mL Amplimune. In both experiments the total RNA was extracted at 0 h, 6 h and 24 h following stimulation. Ribosomal RNA depleted samples were sequenced, and data analysed to determine differential gene expression profiles. Differential gene expression was further analysed to determine enriched biological processes and pathways and a co-expression network.
Results and conclusion
Amplimune induced dose- and time-dependent gene expression profile changes in bovine peripheral blood mononuclear cells, which were enriched into GO-BP regulation of signalling receptor activity, response to cytokine and inflammatory response. Enriched pathways from KEGG analysis were cytokine-cytokine receptor interaction, IL17 signalling and TNF signalling pathways. Selected genes involved in these processes and pathways included IFNG, IL17A, TNF, IL22 and IL23A. PDE1B, CSF2 and IL36G were identified as the most connected genes in a co-expression network, while the connection between SAA2 and SIGLEC5 was the most important for flow of information within the network. Genes encoding for pro-inflammatory cytokines TNF, IL1B, IL6, IL2, and IL12B, and chemokines CCL3, CCL4 and CCL20 were also upregulated at 6 and 24 h post stimulation, as was the β-defensin gene TAP. These results assist in understanding how mycobacterial cell wall fractions alter immune function and may contribute to our understanding of the immune stimulant response attributed to Amplimune.
{"title":"Characterising the transcriptomic response of bovine peripheral blood mononuclear cells to a mycobacterial cell wall fraction","authors":"A.L. Alexander , E.K. Doyle , P. Alexandre , B.C. Hine , T. Vuocolo , N.M. Andronicos , A. Reverter , I.G. Colditz , A.B. Ingham","doi":"10.1016/j.molimm.2024.11.005","DOIUrl":"10.1016/j.molimm.2024.11.005","url":null,"abstract":"<div><h3>Background</h3><div>Innate immune stimulants, including mycobacterium cell wall fractions (MCWF), offer an alternative control option to prevent and treat disease in livestock, by appropriately augmenting the innate immune response. However, the functional response to mycobacterium cell wall fractions in cattle is not well defined. In this study we report the transcriptomic response of bovine peripheral blood mononuclear cells to MCWF in the product Amplimune®.</div></div><div><h3>Methods</h3><div>Amplimune-induced transcriptomic changes in bovine peripheral blood mononuclear cells were determined following an initial pilot study and a later time course experiment. These cells were cultured <em>in vitro</em> for 24 h. In the pilot experiment, cells were stimulated with 0, 2, 5, 12.5 or 31.25 µg/mL Amplimune. In the time course experiment, cells were stimulated with 0 or 31.25 µg/mL Amplimune. In both experiments the total RNA was extracted at 0 h, 6 h and 24 h following stimulation. Ribosomal RNA depleted samples were sequenced, and data analysed to determine differential gene expression profiles. Differential gene expression was further analysed to determine enriched biological processes and pathways and a co-expression network.</div></div><div><h3>Results and conclusion</h3><div>Amplimune induced dose- and time-dependent gene expression profile changes in bovine peripheral blood mononuclear cells, which were enriched into GO-BP regulation of signalling receptor activity, response to cytokine and inflammatory response. Enriched pathways from KEGG analysis were cytokine-cytokine receptor interaction, IL17 signalling and TNF signalling pathways. Selected genes involved in these processes and pathways included <em>IFNG, IL17A, TNF, IL22</em> and <em>IL23A</em>. <em>PDE1B, CSF2</em> and <em>IL36G</em> were identified as the most connected genes in a co-expression network, while the connection between <em>SAA2</em> and <em>SIGLEC5</em> was the most important for flow of information within the network. Genes encoding for pro-inflammatory cytokines <em>TNF, IL1B, IL6, IL2,</em> and <em>IL12B</em>, and chemokines <em>CCL3, CCL4</em> and <em>CCL20</em> were also upregulated at 6 and 24 h post stimulation, as was the β-defensin gene <em>TAP</em>. These results assist in understanding how mycobacterial cell wall fractions alter immune function and may contribute to our understanding of the immune stimulant response attributed to Amplimune.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"176 ","pages":"Pages 37-48"},"PeriodicalIF":3.2,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142682103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-19DOI: 10.1016/j.molimm.2024.11.001
Jing Liu , Yanbo Wang , Zhihui Qu , Junzhuo Si , Yanfang Jiang
Follicular helper T (Tfh) cells have been implicated in the pathophysiology of numerous diseases. This study investigated the hypothetical function of peripheral blood IL-21+ Tfh cells in the etiology of focal segmental glomerulosclerosis (FSGS). Tfh cell subsets were identified via flow cytometry in PBMCs from 15 patients with FSGS and 9 healthy controls (HCs). Moreover, a cytometric bead array (CBA) was used to determine the level of IL-21 in the serum. The proportions of IL-21+ cTfh cells, IL-21+ PD-1+ cTfh cells and serum IL-21 were lower in FSGS patients than in HCs. In FSGS patients, the serum IL-21 concentration was positively correlated with the frequency of IL-21+ cTfh cells and IL-21+ PD-1+ cTfh cells. The frequencies of IL-21+ cTfh cells and IL-21+ PD-1+ cTfh cells were negatively associated with 24-h urine protein but positively correlated with eGFR, serum albumin and serum IgG.
Conclusions
An aberrant frequency of IL-21+ Tfh cells was detected in FSGS patients, which may provide a better understanding of FSGS pathogenesis.
{"title":"Aberrant frequency of circulating IL-21+ T follicular helper cells in patients with primary focal segmental glomerulosclerosis","authors":"Jing Liu , Yanbo Wang , Zhihui Qu , Junzhuo Si , Yanfang Jiang","doi":"10.1016/j.molimm.2024.11.001","DOIUrl":"10.1016/j.molimm.2024.11.001","url":null,"abstract":"<div><div>Follicular helper T (Tfh) cells have been implicated in the pathophysiology of numerous diseases. This study investigated the hypothetical function of peripheral blood IL-21+ Tfh cells in the etiology of focal segmental glomerulosclerosis (FSGS). Tfh cell subsets were identified via flow cytometry in PBMCs from 15 patients with FSGS and 9 healthy controls (HCs). Moreover, a cytometric bead array (CBA) was used to determine the level of IL-21 in the serum. The proportions of IL-21+ cTfh cells, IL-21+ PD-1+ cTfh cells and serum IL-21 were lower in FSGS patients than in HCs. In FSGS patients, the serum IL-21 concentration was positively correlated with the frequency of IL-21+ cTfh cells and IL-21+ PD-1+ cTfh cells. The frequencies of IL-21+ cTfh cells and IL-21+ PD-1+ cTfh cells were negatively associated with 24-h urine protein but positively correlated with eGFR, serum albumin and serum IgG.</div></div><div><h3>Conclusions</h3><div>An aberrant frequency of IL-21+ Tfh cells was detected in FSGS patients, which may provide a better understanding of FSGS pathogenesis.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"176 ","pages":"Pages 30-36"},"PeriodicalIF":3.2,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-18DOI: 10.1016/j.molimm.2024.11.003
Bo Zhou , Jiahui Xue , Jing Wang , Donghua Yu , Fangling Zhou , Jin-ao Duan , Yang Niu , Hanqing Wang
Amygdalins (AMY) from bitter almonds are distinguished by their anti-inflammatory, antibacterial and antioxidant properties, but their role in the treatment of acute lung injury (ALI) and their mechanisms need to be clarified. We sought to investigate whether AMY provides protection against lipopolysaccharide (LPS)-induced ALI in mice and explore the mechanisms of its protection. Results showed that AMY effectively alleviated LPS-induced ALI in a dose-dependent manner by reducing in vivo lung wet/dry ratio, lung/body weight ratio, and myeloperoxidase (MPO). In addition, AMY can significantly reduce lung histopathological injury, decreased bronchoalveolar lavage fluid (BALF) lymphocyte, neutrophil, and monocyte numbers, and decreased the secretion of inflammatory cytokines IL-6, IL-1β, and TNF-α. Through transcriptome sequencing, AMY was found to effectively reduce the mRNA level of CD5L in mice. In AAV-CD5L transfected mice, CD5L overexpression was found to block the protective effect of AMY in LPS-induced ALI mice. It was revealed that AMY inhibited NF-κB entry into the nucleus to reduce iNOS by targeting CD5L. Taken together, AMY can effectively reduce lung inflammation and alleviate ALI, and is a potential novel protective agent against LPS-induced ALI.
{"title":"Amygdalin alleviates LPS-induced acute lung injury in mice by targeting CD5L/iNOS pathway","authors":"Bo Zhou , Jiahui Xue , Jing Wang , Donghua Yu , Fangling Zhou , Jin-ao Duan , Yang Niu , Hanqing Wang","doi":"10.1016/j.molimm.2024.11.003","DOIUrl":"10.1016/j.molimm.2024.11.003","url":null,"abstract":"<div><div>Amygdalins (AMY) from bitter almonds are distinguished by their anti-inflammatory, antibacterial and antioxidant properties, but their role in the treatment of acute lung injury (ALI) and their mechanisms need to be clarified. We sought to investigate whether AMY provides protection against lipopolysaccharide (LPS)-induced ALI in mice and explore the mechanisms of its protection. Results showed that AMY effectively alleviated LPS-induced ALI in a dose-dependent manner by reducing <em>in vivo</em> lung wet/dry ratio, lung/body weight ratio, and myeloperoxidase (MPO). In addition, AMY can significantly reduce lung histopathological injury, decreased bronchoalveolar lavage fluid (BALF) lymphocyte, neutrophil, and monocyte numbers, and decreased the secretion of inflammatory cytokines IL-6, IL-1β, and TNF-α. Through transcriptome sequencing, AMY was found to effectively reduce the mRNA level of CD5L in mice. In AAV-CD5L transfected mice, CD5L overexpression was found to block the protective effect of AMY in LPS-induced ALI mice. It was revealed that AMY inhibited NF-κB entry into the nucleus to reduce iNOS by targeting CD5L. Taken together, AMY can effectively reduce lung inflammation and alleviate ALI, and is a potential novel protective agent against LPS-induced ALI.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"176 ","pages":"Pages 22-29"},"PeriodicalIF":3.2,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-15DOI: 10.1016/j.molimm.2024.10.004
Junjuan Wang , Mengzhen Hao , QianWei Wang , Manman Liu , Guirong Liu , Shiwen Han , Xiaoyan Zhao , Huilian Che
Conformational epitopes are associated with the development of food allergic tolerance and the severity of food allergy. Peanut can trigger severe anaphylactic reactions, however, the reason behind the severe allergic reactions caused by peanut remains unexplained. The purpose of this article was to provide an explanation for the severe allergy caused by peanut, focusing on the conformational epitopes of Ara h 5 and Ara h 8 allergens that exhibit cross-reactivity with asthma reactions. Ara h 5 and Ara h 8 proteins were prepared by an Escherichia coli expression system. IgE reactivity of 37 patients with allergy toward Ara h 5 and Ara h 8 allergens was assessed by using IgE-binding assays, dot blot and western blot. The allergenicity of Ara h 5 and Ara h 8 protein was analysed in mouse model. Conformational IgE epitopes of Ara h 5 was identified using phage peptide library and the Pepitope Server. Compared to Ara h 8, the conformational epitope of Ara h 5 protein was crucial in the process of sensitization. Ara h 5 showed a stronger IgE reactivity and the ability to induce β-hexosaminidase release. Ara h 5 caused more severe lung inflammation than Ara h 8 protein. While Ara h 8 caused more severe intestinal inflammation than Ara h 5. The results showed that the conformational epitope sequences of Ara h 5 were WETIYSR and FHWWYLK. The results provide a theoretical basis for the production of hypoallergenic peanut protein and the immunotherapy of peanut allergy.
构象表位与食物过敏耐受性的形成和食物过敏的严重程度有关。花生可引发严重的过敏反应，但花生引起严重过敏反应的原因至今仍未解释。本文的目的是解释花生引起的严重过敏反应，重点研究与哮喘反应呈交叉反应的 Ara h 5 和 Ara h 8 过敏原的构象表位。Ara h 5 和 Ara h 8 蛋白由大肠杆菌表达系统制备。使用 IgE 结合测定法、点印迹法和免疫印迹法评估了 37 名过敏症患者对 Ara h 5 和 Ara h 8 过敏原的 IgE 反应性。在小鼠模型中分析了 Ara h 5 和 Ara h 8 蛋白的过敏性。利用噬菌体肽库和 Pepitope 服务器鉴定了 Ara h 5 的 IgE 表位构象。与 Ara h 8 相比，Ara h 5 蛋白的构象表位在致敏过程中至关重要。Ara h 5表现出更强的IgE反应性和诱导β-己糖胺酸酶释放的能力。与 Ara h 8 蛋白相比，Ara h 5 引起的肺部炎症更为严重。而 Ara h 8 引起的肠炎比 Ara h 5 更严重。结果表明，Ara h 5 的构象表位序列为 WETIYSR 和 FHWWYLK。这些结果为生产低过敏性花生蛋白和花生过敏的免疫疗法提供了理论依据。
{"title":"The conformational epitope of Ara h 5 was crucial to the severe reactivity of peanut allergy","authors":"Junjuan Wang , Mengzhen Hao , QianWei Wang , Manman Liu , Guirong Liu , Shiwen Han , Xiaoyan Zhao , Huilian Che","doi":"10.1016/j.molimm.2024.10.004","DOIUrl":"10.1016/j.molimm.2024.10.004","url":null,"abstract":"<div><div>Conformational epitopes are associated with the development of food allergic tolerance and the severity of food allergy. Peanut can trigger severe anaphylactic reactions, however, the reason behind the severe allergic reactions caused by peanut remains unexplained. The purpose of this article was to provide an explanation for the severe allergy caused by peanut, focusing on the conformational epitopes of Ara h 5 and Ara h 8 allergens that exhibit cross-reactivity with asthma reactions. Ara h 5 and Ara h 8 proteins were prepared by an Escherichia coli expression system. IgE reactivity of 37 patients with allergy toward Ara h 5 and Ara h 8 allergens was assessed by using IgE-binding assays, dot blot and western blot. The allergenicity of Ara h 5 and Ara h 8 protein was analysed in mouse model. Conformational IgE epitopes of Ara h 5 was identified using phage peptide library and the Pepitope Server. Compared to Ara h 8, the conformational epitope of Ara h 5 protein was crucial in the process of sensitization. Ara h 5 showed a stronger IgE reactivity and the ability to induce β-hexosaminidase release. Ara h 5 caused more severe lung inflammation than Ara h 8 protein. While Ara h 8 caused more severe intestinal inflammation than Ara h 5. The results showed that the conformational epitope sequences of Ara h 5 were WETIYSR and FHWWYLK. The results provide a theoretical basis for the production of hypoallergenic peanut protein and the immunotherapy of peanut allergy.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"176 ","pages":"Pages 11-21"},"PeriodicalIF":3.2,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-07DOI: 10.1016/j.molimm.2024.10.006
Huizhong Li , Fei Wang , Haifang Zhao , Jiale Cao , Shiyuan Wang , Hongxia Li , Barbara Savoldo , Enyu Rao , Gianpietro Dotti , Hongwei Du
B7-H3 is a type I transmembrane protein that belongs to the B7 immune checkpoint protein family, is aberrantly expressed in cancer cells, but rarely expressed in normal tissues, making it an attractive target for cancer therapy. Here, we found B7-H3 is highly expressed in the renal cell carcinoma (RCC) tumor tissues and RCC cell lines, but is undetectable in normal renal tissues. Therefore, we engineered second-generation CAR-T cells targeting B7-H3, incorporating either CD28 or 4–1BB co-stimulatory domains. Both CAR-T cell variants demonstrated potent antitumor activity against RCC tumors in vitro and in metastatic and orthotopic RCC mouse models. Furthermore, the B7-H3 CAR-T cells exhibited remarkable proliferation and robust cytokine release when co-cultured with RCC cancer cells. These findings demonstrated that targeting B7-H3 by CAR-T cells potentially offering a new treatment option for RCC patients.
{"title":"Preclinical assessment of the efficacy of B7-H3 CAR-T in renal cell carcinoma","authors":"Huizhong Li , Fei Wang , Haifang Zhao , Jiale Cao , Shiyuan Wang , Hongxia Li , Barbara Savoldo , Enyu Rao , Gianpietro Dotti , Hongwei Du","doi":"10.1016/j.molimm.2024.10.006","DOIUrl":"10.1016/j.molimm.2024.10.006","url":null,"abstract":"<div><div>B7-H3 is a type I transmembrane protein that belongs to the B7 immune checkpoint protein family, is aberrantly expressed in cancer cells, but rarely expressed in normal tissues, making it an attractive target for cancer therapy. Here, we found B7-H3 is highly expressed in the renal cell carcinoma (RCC) tumor tissues and RCC cell lines, but is undetectable in normal renal tissues. Therefore, we engineered second-generation CAR-T cells targeting B7-H3, incorporating either CD28 or 4–1BB co-stimulatory domains. Both CAR-T cell variants demonstrated potent antitumor activity against RCC tumors in vitro and in metastatic and orthotopic RCC mouse models. Furthermore, the B7-H3 CAR-T cells exhibited remarkable proliferation and robust cytokine release when co-cultured with RCC cancer cells. These findings demonstrated that targeting B7-H3 by CAR-T cells potentially offering a new treatment option for RCC patients.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"176 ","pages":"Pages 1-10"},"PeriodicalIF":3.2,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.molimm.2024.10.003
Hongqin You , Yixin Wang , Xiaokun Wang , Huifang Zhu , Yajie Zhao , Peng Qin , Xue Liu , Mengyu Zhang , Xiaomin Fu , Benling Xu , Yong Zhang , Zibing Wang , Quanli Gao
{"title":"Corrigendum to “CD69+ Vδ1γδ T cells are anti-tumor subpopulations in hepatocellular carcinoma” [Mol. Immunol. 172 (2024) 76–84]","authors":"Hongqin You , Yixin Wang , Xiaokun Wang , Huifang Zhu , Yajie Zhao , Peng Qin , Xue Liu , Mengyu Zhang , Xiaomin Fu , Benling Xu , Yong Zhang , Zibing Wang , Quanli Gao","doi":"10.1016/j.molimm.2024.10.003","DOIUrl":"10.1016/j.molimm.2024.10.003","url":null,"abstract":"","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"175 ","pages":"Page 164"},"PeriodicalIF":3.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.molimm.2024.10.005
Huan Zhang , Zhentao Zhang , Kedi Fan , Yuxi Chen , Peng Xu , Yufan Guo , Xingbo Mo
Functional genes within genomic loci associated with systemic lupus erythematosus (SLE), as identified by genome-wide association studies, exhibit cell-specific characteristics. This study delves into the impact of genetic variants within SLE loci on gene expression in different types of immune cells, unraveling the complex interplay between genetics and immunopathogenesis. Through the integration of genetic association and single-cell transcriptomic sequencing data, we identified potential cell-specific susceptibility genes for SLE across diverse immune cell subsets. The single-cell eQTL analysis revealed 30,409 associations involving 3583 SLE-associated SNPs. These SNPs exhibited associations with expression levels of 147 genes across 14 distinct cell types. The single-cell summary data-based Mendelian randomization (SMR) analysis identified 119 significant associations between the expression levels of 44 genes and SLE. Notably, myeloid cells exhibited associations solely within the MHC region, while T, B, and natural killer cells showed associations with both MHC and non-MHC genes in relation to SLE. Analysis of single-cell transcriptomic data from 33 children SLE cases and 11 match controls (227,303 cells), as well as 7 adult SLE cases and 5 match controls (78,414 cells) highlights differential expression of key genes. Notably, genetic variants within HLA-DRB1, HLA-DRB5, HLA-DQA1, HLA-DQB1, IRF7, IRF5, BLK and HLA-DPA1 play a pivotal role in mediating immune dysregulation in specific immune cell types. Our study contributes to a comprehensive understanding of the intricate relationships between genetics, gene expression and SLE susceptibility. The findings shed light on the cell-specific impacts of genetic variants within SLE-associated genomic loci.
{"title":"Deciphering cell-specific genetic insights: Unraveling the immunogenetic landscape of systemic lupus erythematosus","authors":"Huan Zhang , Zhentao Zhang , Kedi Fan , Yuxi Chen , Peng Xu , Yufan Guo , Xingbo Mo","doi":"10.1016/j.molimm.2024.10.005","DOIUrl":"10.1016/j.molimm.2024.10.005","url":null,"abstract":"<div><div>Functional genes within genomic loci associated with systemic lupus erythematosus (SLE), as identified by genome-wide association studies, exhibit cell-specific characteristics. This study delves into the impact of genetic variants within SLE loci on gene expression in different types of immune cells, unraveling the complex interplay between genetics and immunopathogenesis. Through the integration of genetic association and single-cell transcriptomic sequencing data, we identified potential cell-specific susceptibility genes for SLE across diverse immune cell subsets. The single-cell eQTL analysis revealed 30,409 associations involving 3583 SLE-associated SNPs. These SNPs exhibited associations with expression levels of 147 genes across 14 distinct cell types. The single-cell summary data-based Mendelian randomization (SMR) analysis identified 119 significant associations between the expression levels of 44 genes and SLE. Notably, myeloid cells exhibited associations solely within the MHC region, while T, B, and natural killer cells showed associations with both MHC and non-MHC genes in relation to SLE. Analysis of single-cell transcriptomic data from 33 children SLE cases and 11 match controls (227,303 cells), as well as 7 adult SLE cases and 5 match controls (78,414 cells) highlights differential expression of key genes. Notably, genetic variants within <em>HLA-DRB1</em>, <em>HLA-DRB5</em>, <em>HLA-DQA1</em>, <em>HLA-DQB1</em>, <em>IRF7</em>, <em>IRF5</em>, <em>BLK</em> and <em>HLA-DPA1</em> play a pivotal role in mediating immune dysregulation in specific immune cell types. Our study contributes to a comprehensive understanding of the intricate relationships between genetics, gene expression and SLE susceptibility. The findings shed light on the cell-specific impacts of genetic variants within SLE-associated genomic loci.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"175 ","pages":"Pages 165-175"},"PeriodicalIF":3.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-21DOI: 10.1016/j.molimm.2024.10.001
Bin Wang , Shuqi Feng , Yixuan Jiang , Yufei Tang , Yi Man , Na Wei , Lin Xiang
Dental implants are considered a superior option for the replacement of missing teeth. However, the invasive nature of the surgical procedure often results in significant postoperative inflammation, and the prolonged healing period of 3–6 months presents a notable disadvantage. High mobility group box 1 (HMGB1) is a critical mediator of acute inflammation following surgical injury, which can hinder the onset of osseointegration. This study aims to examine whether the inhibition of HMGB1 can mitigate acute inflammation and subsequently enhance osseointegration. The findings indicate that HMGB1 inhibition markedly reduces inflammation and promotes bone repair in murine models. Further in vitro investigations into the regulatory mechanisms of HMGB1 in macrophages reveal its role in increasing Yes-associated protein (YAP) activity, which contributes to pro-inflammatory polarization. Additionally, conditioned media derived from macrophages influenced by HMGB1 significantly impair the migratory and osteogenic capabilities of bone marrow-derived mesenchymal stem cells, which are essential for bone regeneration. In vivo experiments further validate that the administration of exogenous HMGB1 exacerbates postoperative acute inflammation and obstructs osseointegration. The study concludes that inhibiting HMGB1 fosters an anti-inflammatory polarization of macrophages, leading to diminished postoperative acute inflammation and expedited osseointegration around dental implants in mice.
{"title":"Early anti-inflammatory polarization of macrophages ameliorates post-surgical inflammation and osseointegration around titanium implants in mice","authors":"Bin Wang , Shuqi Feng , Yixuan Jiang , Yufei Tang , Yi Man , Na Wei , Lin Xiang","doi":"10.1016/j.molimm.2024.10.001","DOIUrl":"10.1016/j.molimm.2024.10.001","url":null,"abstract":"<div><div>Dental implants are considered a superior option for the replacement of missing teeth. However, the invasive nature of the surgical procedure often results in significant postoperative inflammation, and the prolonged healing period of 3–6 months presents a notable disadvantage. High mobility group box 1 (HMGB1) is a critical mediator of acute inflammation following surgical injury, which can hinder the onset of osseointegration. This study aims to examine whether the inhibition of HMGB1 can mitigate acute inflammation and subsequently enhance osseointegration. The findings indicate that HMGB1 inhibition markedly reduces inflammation and promotes bone repair in murine models. Further in vitro investigations into the regulatory mechanisms of HMGB1 in macrophages reveal its role in increasing Yes-associated protein (YAP) activity, which contributes to pro-inflammatory polarization. Additionally, conditioned media derived from macrophages influenced by HMGB1 significantly impair the migratory and osteogenic capabilities of bone marrow-derived mesenchymal stem cells, which are essential for bone regeneration. In vivo experiments further validate that the administration of exogenous HMGB1 exacerbates postoperative acute inflammation and obstructs osseointegration. The study concludes that inhibiting HMGB1 fosters an anti-inflammatory polarization of macrophages, leading to diminished postoperative acute inflammation and expedited osseointegration around dental implants in mice.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"175 ","pages":"Pages 155-163"},"PeriodicalIF":3.2,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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