Discovery immunology最新文献_第5页

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}

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Discovery Immunology, a new Open Access journal from the British Society for Immunology 《发现免疫学》是英国免疫学学会的一份新的开放获取期刊

Discovery immunology Pub Date : 2022-01-01 DOI: 10.1093/discim/kyab002

S. Milling

引用次数: 0