Discovery immunology最新文献_第5页

The association of microbial infection and adaptive immune cell activation in Alzheimer’s Disease 阿尔茨海默病中微生物感染与适应性免疫细胞激活的关系

Discovery immunology Pub Date : 2023-01-01 DOI: 10.1093/discim/kyad015

Mathew Clement

{"title":"The association of microbial infection and adaptive immune cell activation in Alzheimer’s Disease","authors":"Mathew Clement","doi":"10.1093/discim/kyad015","DOIUrl":"https://doi.org/10.1093/discim/kyad015","url":null,"abstract":"Summary Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the most common form of dementia. Early symptoms include the loss of memory and mild cognitive ability; however, as the disease progresses, these symptoms can present with increased severity manifesting as mood and behaviour changes, disorientation, and a loss of motor/body control. AD is one of the leading causes of death in the UK, and with an ever-increasing ageing society, patient numbers are predicted to rise posing a significant global health emergency. AD is a complex neurophysiological disorder where pathology is characterized by the deposition and aggregation of misfolded amyloid-beta (Aβ)-protein that in-turn promotes excessive tau-protein production which together drives neuronal cell dysfunction, neuroinflammation, and neurodegeneration. It is widely accepted that AD is driven by a combination of both genetic and immunological processes with recent data suggesting that adaptive immune cell activity within the parenchyma occurs throughout disease. The mechanisms behind these observations remain unclear but suggest that manipulating the adaptive immune response during AD may be an effective therapeutic strategy. Using immunotherapy for AD treatment is not a new concept as the only two approved treatments for AD use antibody-based approaches to target Aβ. However, these have been shown to only temporarily ease symptoms or slow progression highlighting the urgent need for newer treatments. This review discusses the role of the adaptive immune system during AD, how microbial infections may be contributing to inflammatory immune activity and suggests how adaptive immune processes can pose as therapeutic targets for this devastating disease.","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":"45 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135701444","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

The link between T cell activation and development of functionally useful tumour-associated high endothelial venules. T细胞活化与功能有用的肿瘤相关高内皮小静脉发育之间的联系。

Discovery immunology Pub Date : 2023-01-01 DOI: 10.1093/discim/kyad006

Stefan Milutinovic, Awen Gallimore

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Time to treat the climate and nature crisis as one indivisible global health emergency 是时候将气候和自然危机视为一个不可分割的全球卫生紧急事件

Discovery immunology Pub Date : 2023-01-01 DOI: 10.1093/discim/kyad020

Kamran Abbasi, Parveen Ali, Virginia Barbour, Thomas Benfield, Kirsten Bibbins-Domingo, Stephen Hancocks, Richard Horton, Laurie Laybourn-Langton, Robert Mash, Peush Sahni, Wadeia Mohammad Sharief, Paul Yonga, Chris Zielinski

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A novel in vitro model of the small intestinal epithelium in co-culture with “gut-like” dendritic cells 小肠上皮与“肠样”树突状细胞共培养的新型体外模型

Discovery immunology Pub Date : 2023-01-01 DOI: 10.1093/discim/kyad018

Luke J Johnston, Liam Barningham, Eric L Campbell, Vuk Cerovic, Carrie A Duckworth, Lisa Luu, Jonathan Wastling, Hayley Derricott, Janine L Coombes

{"title":"A novel in vitro model of the small intestinal epithelium in co-culture with “gut-like” dendritic cells","authors":"Luke J Johnston, Liam Barningham, Eric L Campbell, Vuk Cerovic, Carrie A Duckworth, Lisa Luu, Jonathan Wastling, Hayley Derricott, Janine L Coombes","doi":"10.1093/discim/kyad018","DOIUrl":"https://doi.org/10.1093/discim/kyad018","url":null,"abstract":"Abstract Cross-talk between dendritic cells (DCs) and the intestinal epithelium is important in the decision to mount a protective immune response to a pathogen or to regulate potentially damaging responses to food antigens and the microbiota. Failures in this decision-making process contribute to the development of intestinal inflammation, making the molecular signals that pass between DCs and intestinal epithelial cells potential therapeutic targets. Until now, in vitro models with sufficient complexity to understand these interactions have been lacking. Here, we outline the development of a co-culture model of in vitro differentiated ‘gut-like’ DCs with small intestinal organoids (enteroids). Sequential exposure of murine bone marrow progenitors to Flt3L, granulocyte macrophage colony-stimulating factor (GM-CSF) and all-trans-retinoic acid (RA) resulted in the generation of a distinct population of conventional DCs expressing CD11b+SIRPα+CD103+/− (cDC2) exhibiting retinaldehyde dehydrogenase (RALDH) activity. These ‘gut-like’ DCs extended transepithelial dendrites across the intact epithelium of enteroids. ‘Gut-like’ DC in co-culture with enteroids can be utilized to define how epithelial cells and cDCs communicate in the intestine under a variety of different physiological conditions, including exposure to different nutrients, natural products, components of the microbiota, or pathogens. Surprisingly, we found that co-culture with enteroids resulted in a loss of RALDH activity in ‘gut-like’ DCs. Continued provision of GM-CSF and RA during co-culture was required to oppose putative negative signals from the enteroid epithelium. Our data contribute to a growing understanding of how intestinal cDCs assess environmental conditions to ensure appropriate activation of the immune response.","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":"37 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136053190","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}

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Metabolic regulation of γδ intraepithelial lymphocytes. γδ上皮内淋巴细胞的代谢调节

Discovery immunology Pub Date : 2023-01-01 Epub Date: 2023-08-10 DOI: 10.1093/discim/kyad011

Sara Alonso, Karen Edelblum

{"title":"Metabolic regulation of γδ intraepithelial lymphocytes.","authors":"Sara Alonso, Karen Edelblum","doi":"10.1093/discim/kyad011","DOIUrl":"10.1093/discim/kyad011","url":null,"abstract":"Elucidating the relationship between cellular metabolism and T cell function has substantially advanced our understanding of how T cells are regulated in response to activation. The metabolic profiles of circulating or peripheral T cells have been well-described, yet less is known regarding how complex local microenvironments shape or modulate the bioenergetic profile of tissue-resident T lymphocytes. Intraepithelial lymphocytes expressing the γδ T cell receptor (γδ IEL) provide immunosurveillance of the intestinal epithelium to limit tissue injury and microbial invasion; however, their activation and effector responses occur independently of antigen recognition. In this review, we will summarize the current knowledge regarding γδ T cell and IEL metabolic profiles and how this informs our understanding of γδ IEL metabolism. We will also discuss the role of the gut microbiota in shaping the metabolic profile of these sentinel lymphocytes, and in turn, how these bioenergetics contribute to regulation of γδ IEL surveillance behavior and effector function. Improved understanding of the metabolic processes involved in γδ IEL homeostasis and function may yield novel strategies to amplify the protective functions of these cells in the context of intestinal health and disease.","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10766425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44885219","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

Discovery Immunology 2023. Highlights from our first full year Discovery Immunology 2023。我们第一年的亮点

Discovery immunology Pub Date : 2023-01-01 DOI: 10.1093/discim/kyad019

Simon Milling

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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

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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}

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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