Discovery immunology最新文献_第3页

Rab46: a novel player in mast cell function. Rab46：肥大细胞功能的新参与者。

Discovery immunology Pub Date : 2023-12-22 eCollection Date: 2024-01-01 DOI: 10.1093/discim/kyad028

Lucia Pedicini, Jessica Smith, Sinisa Savic, Lynn McKeown

{"title":"Rab46: a novel player in mast cell function.","authors":"Lucia Pedicini, Jessica Smith, Sinisa Savic, Lynn McKeown","doi":"10.1093/discim/kyad028","DOIUrl":"https://doi.org/10.1093/discim/kyad028","url":null,"abstract":"Mast cells are infamous for mediating allergic and inflammatory diseases due to their capacity of rapidly releasing a wide range of inflammatory mediators stored in cytoplasmic granules. However, mast cells also have several important physiological roles that involve selective and agonist-specific release of these active mediators. While a filtering mechanism at the plasma membrane could regulate the selective release of some cargo, the plethora of stored cargo and the diversity of mast cell functions suggests the existence of granule subtypes with distinct trafficking pathways. The molecular mechanisms underlying differential trafficking and exocytosis of these granules are not known, neither is it clear how granule trafficking is coupled to the stimulus. In endothelial cells, a Rab GTPase, Rab46, responds to histamine but not thrombin signals, and this regulates the trafficking of a subpopulation of endothelial-specific granules. Here, we sought to explore, for the first time, if Rab46 plays a role in mast cell function. We demonstrate that Rab46 is highly expressed in human and murine mast cells, and Rab46 genetic deletion has an effect on mast cell degranulation that depends on both stimuli and mast cell subtype. This initial insight into the contribution of Rab46 to mast cell function and the understanding of the role of Rab46 in stimuli-dependent trafficking in other cell types necessitates further investigations of Rab46 in mast cell granular trafficking so that novel and specific therapeutic targets for treatment of the diverse pathologies mediated by mast cells can be developed.","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":"3 1","pages":"kyad028"},"PeriodicalIF":0.0,"publicationDate":"2023-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10917158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140860771","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

The glucocorticoid dexamethasone inhibits HIF-1α stabilization and metabolic reprogramming in lipopolysaccharide-stimulated primary macrophages. 糖皮质激素地塞米松抑制脂多糖刺激的原代巨噬细胞中HIF-1α的稳定和代谢重编程。

Discovery immunology Pub Date : 2023-12-04 eCollection Date: 2023-01-01 DOI: 10.1093/discim/kyad027

Sally A Clayton, Chloe Lockwood, John D O'Neil, Kalbinder K Daley, Sofia Hain, Dina Abdelmottaleb, Oliwia O Bolimowska, Daniel A Tennant, Andrew R Clark

{"title":"The glucocorticoid dexamethasone inhibits HIF-1α stabilization and metabolic reprogramming in lipopolysaccharide-stimulated primary macrophages.","authors":"Sally A Clayton, Chloe Lockwood, John D O'Neil, Kalbinder K Daley, Sofia Hain, Dina Abdelmottaleb, Oliwia O Bolimowska, Daniel A Tennant, Andrew R Clark","doi":"10.1093/discim/kyad027","DOIUrl":"10.1093/discim/kyad027","url":null,"abstract":"Synthetic glucocorticoids are used to treat many chronic and acute inflammatory conditions. Frequent adverse effects of prolonged exposure to glucocorticoids include disturbances of glucose homeostasis caused by changes in glucose traffic and metabolism in muscle, liver, and adipose tissues. Macrophages are important targets for the anti-inflammatory actions of glucocorticoids. These cells rely on aerobic glycolysis to support various pro-inflammatory and antimicrobial functions. Employing a potent pro-inflammatory stimulus in two commonly used model systems (mouse bone marrow-derived and human monocyte-derived macrophages), we showed that the synthetic glucocorticoid dexamethasone inhibited lipopolysaccharide-mediated activation of the hypoxia-inducible transcription factor HIF-1α, a critical driver of glycolysis. In both cell types, dexamethasone-mediated inhibition of HIF-1α reduced the expression of the glucose transporter GLUT1, which imports glucose to fuel aerobic glycolysis. Aside from this conserved response, other metabolic effects of lipopolysaccharide and dexamethasone differed between human and mouse macrophages. These findings suggest that glucocorticoids exert anti-inflammatory effects by impairing HIF-1α-dependent glucose uptake in activated macrophages. Furthermore, harmful and beneficial (anti-inflammatory) effects of glucocorticoids may have a shared mechanistic basis, depending on the alteration of glucose utilization.","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":"2 1","pages":"kyad027"},"PeriodicalIF":0.0,"publicationDate":"2023-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10917182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140861773","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

The generation of senescent-like CD4+ EMRA T cells in T2D and their contribution to poor COVID-19 vaccine responses T2D 中衰老样 CD4+ EMRA T 细胞的生成及其对 COVID-19 疫苗应答不良的贡献

Discovery immunology Pub Date : 2023-11-28 DOI: 10.1093/discim/kyad026

C. Garrod-Ketchley, Laure Mourgue d'Algue, Katie Littlewood, Gillian Hood, Anne Worthington, Melanie Pattrick, Caroline Sutcliffe, Zoi Valla, Noorshad Joti, Udeshi Zalak, Amy Edwards, Sarah Finer, S. Henson

{"title":"The generation of senescent-like CD4+ EMRA T cells in T2D and their contribution to poor COVID-19 vaccine responses","authors":"C. Garrod-Ketchley, Laure Mourgue d'Algue, Katie Littlewood, Gillian Hood, Anne Worthington, Melanie Pattrick, Caroline Sutcliffe, Zoi Valla, Noorshad Joti, Udeshi Zalak, Amy Edwards, Sarah Finer, S. Henson","doi":"10.1093/discim/kyad026","DOIUrl":"https://doi.org/10.1093/discim/kyad026","url":null,"abstract":"CD4+ T cells are essential for protection from viral pathogens, such as SARS-CoV-2. However, an increase in the dysfunction CD4+ EMRA subset is likely to hinder the immune response towards viruses. We show here that CD4+ EMRAs are increased with elevated blood glucose, such as people living with T2D, which alters mitochondrial function and causes the differentiation of CD4+ T cells, reducing the immune response to COVID-19 vaccination. CD4+ T cells were examined for senescence, their insulin dynamics, and mitochondrial function after in vitro culture of high and low glucose media, with or without rotenone or mitoQ. Serum samples were used to assess circulating inflammation and IgG antibodies to SARS-CoV-2. People living with T2D had increased expression of CD4+ EMRA T cells, the appearance of which correlated with increasing blood glucose values. The T2D cohort showed a reduced mitochondrial membrane potential and increased mtROS production. These results were mimicked using high glucose media which accelerated CD4+ T cell differentiation and reduced MMP. People living with T2D (non-hyperglycaemic and hyperglycaemic) had altered expression of inflammatory mediators. CD4+ EMRA cells did not respond to COVID-19 peptides, and people with T2D had a reduced T cell and antibody response to SARS-CoV-2 S1 spike protein. We have shown that senescent-like CD4+ EMRA influence the viral response in SARS-CoV-2 and that CD4+ EMRAs may arise from faulty mitochondrial dynamics due to increased environmental glucose. Further study is required to determine the direct link increased glucose has with CD4+ EMRA formation.","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139216519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

T cell and bacterial microbiota interaction at intestinal and skin epithelial interfaces 肠道和皮肤上皮界面的 T 细胞与细菌微生物群相互作用

Discovery immunology Pub Date : 2023-11-25 DOI: 10.1093/discim/kyad024

Damian Maseda, S. Manfredo-Vieira, Aimee S Payne

引用次数: 0

Gut immune responses and evolution of the gut microbiome – a hypothesis 肠道免疫反应和肠道微生物群的进化--一个假设

Discovery immunology Pub Date : 2023-11-23 DOI: 10.1093/discim/kyad025

Marcus W. Viney, Louise Cheynel

引用次数: 0

RAM is upregulated during T cell activation and is required for RNA cap formation and gene expression RAM 在 T 细胞活化过程中上调，是 RNA 帽形成和基因表达所必需的

Discovery immunology Pub Date : 2023-11-17 DOI: 10.1093/discim/kyad021

Katarzyna Knop, C. Gómez-Moreira, Alison Galloway, Dimitrinka Ditsova, V. Cowling

引用次数: 0

Immunotherapy in the context of immune-specialized environment of brain metastases 脑转移瘤免疫特化环境下的免疫疗法

Discovery immunology Pub Date : 2023-11-16 DOI: 10.1093/discim/kyad023

F. James, M. Lorger

引用次数: 0

Eosinophils in obesity and obesity-associated disorders 嗜酸性粒细胞在肥胖和肥胖相关疾病中的作用

Discovery immunology Pub Date : 2023-11-14 DOI: 10.1093/discim/kyad022

Yanan Hu, Svetoslav Chakarov

引用次数: 0

Pericardial & Mediastinal Fat-Associated Lymphoid Clusters are rapidly activated in an alkane induced model of Systemic Lupus Erythematosus 心包,纵隔脂肪相关淋巴细胞簇在烷烃诱导的系统性红斑狼疮模型中被迅速激活

Discovery immunology Pub Date : 2023-09-25 DOI: 10.1093/discim/kyad017

Karolina Bentkowska, Alex Hardgrave, Nadia Iqbal, Laura Gresty, Bethany Marsden, Sheila Macharia, Lucy Jackson-Jones

{"title":"Pericardial & Mediastinal Fat-Associated Lymphoid Clusters are rapidly activated in an alkane induced model of Systemic Lupus Erythematosus","authors":"Karolina Bentkowska, Alex Hardgrave, Nadia Iqbal, Laura Gresty, Bethany Marsden, Sheila Macharia, Lucy Jackson-Jones","doi":"10.1093/discim/kyad017","DOIUrl":"https://doi.org/10.1093/discim/kyad017","url":null,"abstract":"Abstract Systemic Lupus Erythematosus (SLE) is an autoimmune disease predominated by auto-antibodies that recognise cellular components. Pleural involvement is the most common SLE-related lung disease. Natural antibodies are rapidly secreted by innate-like B cells following perturbation of homeostasis and are important in the early stages of immune activation. The serous cavities are home to large numbers of innate-like B cells present both within serous fluid and resident within fat-associated lymphoid clusters (FALCs). FALCs are important hubs for B-cell activation and local antibody secretion within the body cavities. Patients with SLE can develop anti-phospholipid antibodies and in rare situations develop alveolar haemorrhage. Utilising delivery of the hydrocarbon oil pristane in C57BL/6 mice as a model of SLE we identify a rapid expansion of pleural cavity B cells as early as day 3 after intra-peritoneal pristane delivery. Following pristane delivery, pericardial B1 B cells are proliferative, express the plasma-cell surface marker CD138 and secrete both innate and class switched antibodies highlighting that this cavity niche may play an unrecognised role in the initiation of lupus pleuritis.","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":"8 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135864884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Conventional and non-conventional antigen presentation by mast cells 肥大细胞的常规和非常规抗原呈递

Discovery immunology Pub Date : 2023-09-19 DOI: 10.1093/discim/kyad016

Chi-Ching Tung, Abhay P S Rathore, Ashley L St. John

引用次数: 0