Discovery immunology最新文献_第7页

Review: Unravelling the Role of DNA Sensing in Alum Adjuvant Activity. 综述：揭示DNA传感在明矾佐剂活性中的作用

Discovery immunology Pub Date : 2022-12-29 eCollection Date: 2023-01-01 DOI: 10.1093/discim/kyac012

Zara Gatt, Utku Gunes, Arianna Raponi, Larissa Camargo da Rosa, James M Brewer

引用次数: 0

Nur77-Tempo mice reveal T cell steady state antigen recognition. Nur77-Tempo小鼠显示了T细胞稳态抗原识别能力。

Discovery immunology Pub Date : 2022-12-22 DOI: 10.1093/discim/kyac009

Thomas A E Elliot, Emma K Jennings, David A J Lecky, Sophie Rouvray, Gillian M Mackie, Lisa Scarfe, Lozan Sheriff, Masahiro Ono, Kendle M Maslowski, David Bending

{"title":"Nur77-Tempo mice reveal T cell steady state antigen recognition.","authors":"Thomas A E Elliot, Emma K Jennings, David A J Lecky, Sophie Rouvray, Gillian M Mackie, Lisa Scarfe, Lozan Sheriff, Masahiro Ono, Kendle M Maslowski, David Bending","doi":"10.1093/discim/kyac009","DOIUrl":"10.1093/discim/kyac009","url":null,"abstract":"In lymphocytes, Nr4a gene expression is specifically regulated by antigen receptor signalling, making them ideal targets for use as distal T cell receptor (TCR) reporters. Nr4a3-Timer of cell kinetics and activity (Tocky) mice are a ground-breaking tool to report TCR-driven Nr4a3 expression using Fluorescent Timer protein (FT). FT undergoes a time-dependent shift in its emission spectrum following translation, allowing for the temporal reporting of transcriptional events. Our recent work suggested that Nr4a1/Nur77 may be a more sensitive gene to distal TCR signals compared to Nr4a3, so we, therefore, generated Nur77-Timer-rapidly-expressed-in-lymphocytes (Tempo) mice that express FT under the regulation of Nur77. We validated the ability of Nur77-Tempo mice to report TCR and B cell receptor signals and investigated the signals regulating Nur77-FT expression. We found that Nur77-FT was sensitive to low-strength TCR signals, and its brightness was graded in response to TCR signal strength. Nur77-FT detected positive selection signals in the thymus, and analysis of FT expression revealed that positive selection signals are often persistent in nature, with most thymic Treg expressing FT Blue. We found that active TCR signals in the spleen are low frequency, but CD69+ lymphoid T cells are enriched for FT Blue+ Red+ T cells, suggesting frequent TCR signalling. In non-lymphoid tissue, we saw a dissociation of FT protein from CD69 expression, indicating that tissue residency is not associated with tonic TCR signals. Nur77-Tempo mice, therefore, combine the temporal dynamics from the Tocky innovation with increased sensitivity of Nr4a1 to lower TCR signal strengths.","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":"1 1","pages":"kyac009"},"PeriodicalIF":0.0,"publicationDate":"2022-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7614040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10630120","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

What do cancer-specific T cells 'see'? 癌症特异性T细胞“看到”了什么？

Discovery immunology Pub Date : 2022-12-06 eCollection Date: 2023-01-01 DOI: 10.1093/discim/kyac011

Sabaria Shah, Abdullah Al-Omari, Katherine W Cook, Samantha J Paston, Lindy G Durrant, Victoria A Brentville

{"title":"What do cancer-specific T cells 'see'?","authors":"Sabaria Shah, Abdullah Al-Omari, Katherine W Cook, Samantha J Paston, Lindy G Durrant, Victoria A Brentville","doi":"10.1093/discim/kyac011","DOIUrl":"10.1093/discim/kyac011","url":null,"abstract":"Complex cellular interactions between the immune system and cancer can impact tumour development, growth, and progression. T cells play a key role in these interactions; however, the challenge for T cells is to recognize tumour antigens whilst minimizing cross-reactivity with antigens associated with healthy tissue. Some tumour cells, including those associated with viral infections, have clear, tumour-specific antigens that can be targeted by T cells. A high mutational burden can lead to increased numbers of mutational neoantigens that allow very specific immune responses to be generated but also allow escape variants to develop. Other cancer indications and those with low mutational burden are less easily distinguished from normal tissue. Recent studies have suggested that cancer-associated alterations in tumour cell biology including changes in post-translational modification (PTM) patterns may also lead to novel antigens that can be directly recognized by T cells. The PTM-derived antigens provide tumour-specific T-cell responses that both escape central tolerance and avoid the necessity for individualized therapies. PTM-specific CD4 T-cell responses have shown tumour therapy in murine models and highlight the importance of CD4 T cells as well as CD8 T cells in reversing the immunosuppressive tumour microenvironment. Understanding which cancer-specific antigens can be recognized by T cells and the way that immune tolerance and the tumour microenvironment shape immune responses to cancer is vital for the future development of cancer therapies.","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":" ","pages":"kyac011"},"PeriodicalIF":0.0,"publicationDate":"2022-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10917189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42238826","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

Bench to Bedside: Modelling Inflammatory Arthritis. 长凳到床边：炎症性关节炎建模

Discovery immunology Pub Date : 2022-11-23 eCollection Date: 2023-01-01 DOI: 10.1093/discim/kyac010

Chiamaka I Chidomere, Mussarat Wahid, Samuel Kemble, Caroline Chadwick, Richard Thomas, Rowan S Hardy, Helen M McGettrick, Amy J Naylor

{"title":"Bench to Bedside: Modelling Inflammatory Arthritis.","authors":"Chiamaka I Chidomere, Mussarat Wahid, Samuel Kemble, Caroline Chadwick, Richard Thomas, Rowan S Hardy, Helen M McGettrick, Amy J Naylor","doi":"10.1093/discim/kyac010","DOIUrl":"10.1093/discim/kyac010","url":null,"abstract":"Inflammatory arthritides such as rheumatoid arthritis are a major cause of disability. Pre-clinical murine models of inflammatory arthritis continue to be invaluable tools with which to identify and validate therapeutic targets and compounds. The models used are well-characterised and, whilst none truly recapitulates the human disease, they are crucial to researchers seeking to identify novel therapeutic targets and to test efficacy during preclinical trials of novel drug candidates. The arthritis parameters recorded during clinical trials and routine clinical patient care have been carefully standardised, allowing comparison between centres, trials, and treatments. Similar standardisation of scoring across in vivo models has not occurred, which makes interpretation of published results, and comparison between arthritis models, challenging. Here, we include a detailed and readily implementable arthritis scoring system, that increases the breadth of arthritis characteristics captured during experimental arthritis and supports responsive and adaptive monitoring of disease progression in murine models of inflammatory arthritis. In addition, we reference the wider ethical and experimental factors researchers should consider during the experimental design phase, with emphasis on the continued importance of replacement, reduction, and refinement of animal usage in arthritis research.","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":" ","pages":"kyac010"},"PeriodicalIF":0.0,"publicationDate":"2022-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10917191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43011284","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

Revealing stromal and lymphoid sources of Col3a1-expression during inflammation using a novel reporter mouse. 使用新型报告小鼠揭示炎症过程中Col3a1表达的基质和淋巴来源

Discovery immunology Pub Date : 2022-11-21 eCollection Date: 2022-01-01 DOI: 10.1093/discim/kyac008

Larissa C da Rosa, Hannah E Scales, Sangeet Makhija, Katie Sutherland, Robert A Benson, James M Brewer, Paul Garside

引用次数: 0

Immune cell involvement in brown adipose tissue functions. 免疫细胞参与棕色脂肪组织功能

Discovery immunology Pub Date : 2022-10-31 eCollection Date: 2022-01-01 DOI: 10.1093/discim/kyac007

Adeline Bertola, Alexandre Gallerand, Stoyan Ivanov

引用次数: 0

The role of interleukin-33 in organ fibrosis. 白细胞介素33在器官纤维化中的作用

Discovery immunology Pub Date : 2022-09-26 eCollection Date: 2022-01-01 DOI: 10.1093/discim/kyac006

Samuele Di Carmine, Molly M Scott, Mairi H McLean, Henry J McSorley

{"title":"The role of interleukin-33 in organ fibrosis.","authors":"Samuele Di Carmine, Molly M Scott, Mairi H McLean, Henry J McSorley","doi":"10.1093/discim/kyac006","DOIUrl":"10.1093/discim/kyac006","url":null,"abstract":"Interleukin (IL)-33 is highly expressed in the nucleus of cells present at barrier sites and signals via the ST2 receptor. IL-33 signalling via ST2 is essential for return to tissue homeostasis after acute inflammation, promoting fibrinogenesis and wound healing at injury sites. However, this wound-healing response becomes aberrant during chronic or sustained inflammation, leading to transforming growth factor beta (TGF-β) release, excessive extracellular matrix deposition, and fibrosis. This review addresses the role of the IL-33 pathway in fibrotic diseases of the lung, liver, gastrointestinal tract, skin, kidney and heart. In the lung and liver, IL-33 release leads to the activation of pro-fibrotic TGF-β, and in these sites, IL-33 has clear pro-fibrotic roles. In the gastrointestinal tract, skin, and kidney, the role of IL-33 is more complex, being both pro-fibrotic and tissue protective. Finally, in the heart, IL-33 serves cardioprotective functions by favouring tissue healing and preventing cardiomyocyte death. Altogether, this review indicates the presence of an unclear and delicate balance between resolving and pro-fibrotic capabilities of IL-33, which has a central role in the modulation of type 2 inflammation and fibrosis in response to tissue injury.","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":" ","pages":"kyac006"},"PeriodicalIF":0.0,"publicationDate":"2022-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10917208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44084725","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

Looking into the IL-1 of the storm: are inflammasomes the link between immunothrombosis and hyperinflammation in cytokine storm syndromes? 风暴中的IL-1：炎症小体是细胞因子风暴综合征中免疫血栓形成和高炎症之间的联系吗？

Discovery immunology Pub Date : 2022-09-14 eCollection Date: 2022-01-01 DOI: 10.1093/discim/kyac005

Tara A Gleeson, Erik Nordling, Christina Kaiser, Catherine B Lawrence, David Brough, Jack P Green, Stuart M Allan

{"title":"Looking into the IL-1 of the storm: are inflammasomes the link between immunothrombosis and hyperinflammation in cytokine storm syndromes?","authors":"Tara A Gleeson, Erik Nordling, Christina Kaiser, Catherine B Lawrence, David Brough, Jack P Green, Stuart M Allan","doi":"10.1093/discim/kyac005","DOIUrl":"10.1093/discim/kyac005","url":null,"abstract":"Inflammasomes and the interleukin (IL)-1 family of cytokines are key mediators of both inflammation and immunothrombosis. Inflammasomes are responsible for the release of the pro-inflammatory cytokines IL-1β and IL-18, as well as releasing tissue factor (TF), a pivotal initiator of the extrinsic coagulation cascade. Uncontrolled production of inflammatory cytokines results in what is known as a \"cytokine storm\" leading to hyperinflammatory disease. Cytokine storms can complicate a variety of diseases and results in hypercytokinemia, coagulopathies, tissue damage, multiorgan failure, and death. Patients presenting with cytokine storm syndromes have a high mortality rate, driven in part by disseminated intravascular coagulation (DIC). While our knowledge on the factors propagating cytokine storms is increasing, how cytokine storm influences DIC remains unknown, and therefore treatments for diseases, where these aspects are a key feature are limited, with most targeting specific cytokines. Currently, no therapies target the immunothrombosis aspect of hyperinflammatory syndromes. Here we discuss how targeting the inflammasome and pyroptosis may be a novel therapeutic strategy for the treatment of hyperinflammation and its associated pathologies.","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":" ","pages":"kyac005"},"PeriodicalIF":0.0,"publicationDate":"2022-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10917224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46924100","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

Stroke-induced changes to immune function and their relevance to increased risk of severe COVID-19 disease. 中风引起的免疫功能变化及其与严重新冠肺炎疾病风险增加的相关性

Discovery immunology Pub Date : 2022-08-11 eCollection Date: 2022-01-01 DOI: 10.1093/discim/kyac004

Laura McCulloch, Isobel C Mouat, Kieron South, Barry W McColl, Stuart M Allan, Craig J Smith

引用次数: 0

Expression of antimicrobial host defence peptides in the central nervous system during health and disease. 健康和疾病期间中枢神经系统抗微生物宿主防御肽的表达

Discovery immunology Pub Date : 2022-07-26 eCollection Date: 2022-01-01 DOI: 10.1093/discim/kyac003

Katie J Smith, Emily Gwyer Findlay

{"title":"Expression of antimicrobial host defence peptides in the central nervous system during health and disease.","authors":"Katie J Smith, Emily Gwyer Findlay","doi":"10.1093/discim/kyac003","DOIUrl":"10.1093/discim/kyac003","url":null,"abstract":"Antimicrobial host defence peptides (HDP) are critical for the first line of defence against bacterial, viral, and fungal pathogens. Over the past decade we have become more aware that, in addition to their antimicrobial roles, they also possess the potent immunomodulatory capacity. This includes chemoattracting immune cells, activating dendritic cells and macrophages, and altering T-cell differentiation. Most examinations of their immunomodulatory roles have focused on tissues in which they are very abundant, such as the intestine and the inflamed skin. However, HDP have now been detected in the brain and the spinal cord during a number of conditions. We propose that their presence in the central nervous system (CNS) during homeostasis, infection, and neurodegenerative disease has the potential to contribute to immunosurveillance, alter host responses and skew developing immunity. Here, we review the evidence for HDP expression and function in the CNS in health and disease. We describe how a wide range of HDP are expressed in the CNS of humans, rodents, birds, and fish, suggesting a conserved role in protecting the brain from pathogens, with evidence of production by resident CNS cells. We highlight differences in methodology used and how this may have resulted in the immunomodulatory roles of HDP being overlooked. Finally, we discuss what HDP expression may mean for CNS immune responses.","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":" ","pages":"kyac003"},"PeriodicalIF":0.0,"publicationDate":"2022-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10917193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49149334","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