Discovery immunology最新文献_第6页

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

NKG2D signaling regulates IL-17A-producing γδT cells in mice to promote cancer progression. NKG2D 信号调节小鼠体内产生 IL-17A 的 γδT 细胞，从而促进癌症进展。

Discovery immunology Pub Date : 2022-05-10 eCollection Date: 2022-01-01 DOI: 10.1093/discim/kyac002

Sophie Curio, Sarah C Edwards, Toshiyasu Suzuki, Jenny McGovern, Chiara Triulzi, Nagisa Yoshida, Gustav Jonsson, Teresa Glauner, Damiano Rami, Robert Wiesheu, Anna Kilbey, Rachel Violet Purcell, Seth B Coffelt, Nadia Guerra

{"title":"NKG2D signaling regulates IL-17A-producing γδT cells in mice to promote cancer progression.","authors":"Sophie Curio, Sarah C Edwards, Toshiyasu Suzuki, Jenny McGovern, Chiara Triulzi, Nagisa Yoshida, Gustav Jonsson, Teresa Glauner, Damiano Rami, Robert Wiesheu, Anna Kilbey, Rachel Violet Purcell, Seth B Coffelt, Nadia Guerra","doi":"10.1093/discim/kyac002","DOIUrl":"10.1093/discim/kyac002","url":null,"abstract":"γδT cells are unconventional T cells particularly abundant in mucosal tissues that play an important role in tissue surveillance, homeostasis, and cancer. γδT cells recognize stressed cells or cancer cells through the NKG2D receptor to kill these cells and maintain normality. Contrary to the well-established anti-tumor function of these NKG2D-expressing γδT cells, we show here that, in mice, NKG2D regulates a population of pro-tumor γδT cells capable of producing IL-17A. Germline deletion of Klrk1, the gene encoding NKG2D, reduced the frequency of γδT cells in the tumor microenvironment and delayed tumor progression. We further show that blocking NKG2D reduced the capability of γδT cells to produce IL-17A in the pre-metastatic lung and that co-culture of lung T cells with NKG2D ligand-expressing tumor cells specifically increased the frequency of γδT cells. Together, these data support the hypothesis that, in a tumor microenvironment where NKG2D ligands are constitutively expressed, γδT cells accumulate in an NKG2D-dependent manner and drive tumor progression by secreting pro-inflammatory cytokines, such as IL-17A.","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":"1 1","pages":"kyac002"},"PeriodicalIF":0.0,"publicationDate":"2022-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0f/df/kyac002.PMC9580227.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9729686","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

Unconventional modes of peptide-HLA-I presentation change the rules of TCR engagement. 肽- hla - 1呈递的非常规模式改变了TCR参与的规则

Discovery immunology Pub Date : 2022-05-04 eCollection Date: 2022-01-01 DOI: 10.1093/discim/kyac001

Jade R Hopkins, Bruce J MacLachlan, Stephen Harper, Andrew K Sewell, David K Cole

{"title":"Unconventional modes of peptide-HLA-I presentation change the rules of TCR engagement.","authors":"Jade R Hopkins, Bruce J MacLachlan, Stephen Harper, Andrew K Sewell, David K Cole","doi":"10.1093/discim/kyac001","DOIUrl":"10.1093/discim/kyac001","url":null,"abstract":"The intracellular proteome of virtually every nucleated cell in the body is continuously presented at the cell surface via the human leukocyte antigen class I (HLA-I) antigen processing pathway. This pathway classically involves proteasomal degradation of intracellular proteins into short peptides that can be presented by HLA-I molecules for interrogation by T-cell receptors (TCRs) expressed on the surface of CD8+ T cells. During the initiation of a T-cell immune response, the TCR acts as the T cell's primary sensor, using flexible loops to mould around the surface of the pHLA-I molecule to identify foreign or dysregulated antigens. Recent findings demonstrate that pHLA-I molecules can also be highly flexible and dynamic, altering their shape according to minor polymorphisms between different HLA-I alleles, or interactions with different peptides. These flexible presentation modes have important biological consequences that can, for example, explain why some HLA-I alleles offer greater protection against HIV, or why some cancer vaccine approaches have been ineffective. This review explores how these recent findings redefine the rules for peptide presentation by HLA-I molecules and extend our understanding of the molecular mechanisms that govern TCR-mediated antigen discrimination.","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":" ","pages":"kyac001"},"PeriodicalIF":0.0,"publicationDate":"2022-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10917088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42028673","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