Discovery immunology最新文献_第5页

Single-cell RNA sequencing of human lung innate lymphoid cells in the vascular and tissue niche reveals molecular features of tissue adaptation. 人肺血管和组织生态位先天淋巴样细胞的单细胞rna测序揭示了组织适应的分子特征

Discovery immunology Pub Date : 2023-06-24 eCollection Date: 2023-01-01 DOI: 10.1093/discim/kyad007

Arlisa Alisjahbana, Imran Mohammad, Yu Gao, Elza Evren, Tim Willinger

{"title":"Single-cell RNA sequencing of human lung innate lymphoid cells in the vascular and tissue niche reveals molecular features of tissue adaptation.","authors":"Arlisa Alisjahbana, Imran Mohammad, Yu Gao, Elza Evren, Tim Willinger","doi":"10.1093/discim/kyad007","DOIUrl":"10.1093/discim/kyad007","url":null,"abstract":"Innate lymphoid cells (ILCs) are sentinels of healthy organ function, yet it is unknown how ILCs adapt to distinct anatomical niches within tissues. Here, we used a unique humanized mouse model, MISTRG mice transplanted with human hematopoietic stem and progenitor cells (HSPCs), to define the gene signatures of human ILCs in the vascular versus the tissue (extravascular) compartment of the lung. Single-cell RNA sequencing in combination with intravascular cell labeling demonstrated that heterogeneous populations of human ILCs and natural killer (NK) cells occupied the vascular and tissue niches in the lung of HSPC-engrafted MISTRG mice. Moreover, we discovered that niche-specific cues shape the molecular programs of human ILCs in the distinct sub-anatomical compartments of the lung. Specifically, extravasation of ILCs into the lung tissue was associated with the upregulation of genes involved in the acquisition of tissue residency, cell positioning within the lung, sensing of tissue-derived signals, cellular stress responses, nutrient uptake, and interaction with other tissue-resident immune cells. We also defined a core tissue signature shared between human ILCs and NK cells in the extravascular space of the lung, consistent with imprinting by signals from the local microenvironment. The molecular characterization of human ILCs and NK cells in the vascular and tissue niches of the lung provides new knowledge on the mechanisms of ILC tissue adaptation and represents a resource for further studies.","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":" ","pages":"kyad007"},"PeriodicalIF":0.0,"publicationDate":"2023-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11034571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41850609","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 wild mouse bone marrow has a unique myeloid and lymphoid composition and phenotype. 野生小鼠骨髓具有独特的髓系和淋巴系组成和表型

Discovery immunology Pub Date : 2023-04-18 eCollection Date: 2023-01-01 DOI: 10.1093/discim/kyad005

Andrew Muir, Alex Bennett, Hannah Smith, Larisa Logunova, Andrew Wolfenden, Jonathan Fenn, Ann E Lowe, Andy Brass, John R Grainger, Joanne E Konkel, Janette E Bradley, Iris Mair, Kathryn J Else

{"title":"The wild mouse bone marrow has a unique myeloid and lymphoid composition and phenotype.","authors":"Andrew Muir, Alex Bennett, Hannah Smith, Larisa Logunova, Andrew Wolfenden, Jonathan Fenn, Ann E Lowe, Andy Brass, John R Grainger, Joanne E Konkel, Janette E Bradley, Iris Mair, Kathryn J Else","doi":"10.1093/discim/kyad005","DOIUrl":"10.1093/discim/kyad005","url":null,"abstract":"The murine bone marrow has a central role in immune function and health as the primary source of leukocytes in adult mice. Laboratory mice provide a human-homologous, genetically manipulable and reproducible model that has enabled an immeasurable volume of high-quality immunological research. However, recent research has questioned the translatability of laboratory mouse research into humans and proposed that the exposure of mice to their wild and natural environment may hold the key to further immunological breakthroughs. To date, there have been no studies providing an in-depth cellular analysis of the wild mouse bone marrow. This study utilized wild mice from an isolated island population (Isle of May, Scotland, UK) and performed flow cytometric and histological analysis to characterize the myeloid, lymphoid, hematopoietic progenitor, and adipocyte compartments within the wild mouse bone marrow. We find that, compared to laboratory mouse bone marrow, the wild mouse bone marrow differs in every cell type assessed. Some of the major distinctions include; a smaller B cell compartment with an enriched presence of plasma cells, increased proportions of KLRG1+ CD8+ T cells, diminished CD11b expression in the myeloid lineage and a five-fold enlargement of the eosinophil compartment. We conclude that the wild mouse bone marrow is dramatically distinct from its laboratory counterparts, with multiple phenotypes that to our knowledge have never been observed in laboratory models. Further research into these unique features may uncover novel immunological mechanisms and grant a greater understanding of the role of the immune system in a natural setting.","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":" ","pages":"kyad005"},"PeriodicalIF":0.0,"publicationDate":"2023-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10917185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44544870","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

Migration of stem-like CD8 T cells between tissue microenvironments underpins successful anti-tumour immune responses. 干性 CD8 T 细胞在组织微环境之间的迁移是成功的抗肿瘤免疫反应的基础。

Discovery immunology Pub Date : 2023-02-18 eCollection Date: 2023-01-01 DOI: 10.1093/discim/kyad004

Bethany C Kennedy, Isaac Dean, David R Withers

引用次数: 0

Twenty-One Flavors of Type 1 Innate Lymphoid Cells with PD-1 (Programmed Cell Death-1 Receptor) Sprinkles. 含有PD-1（程序性细胞死亡-1受体）的21种1型固有淋巴细胞风味

Discovery immunology Pub Date : 2023-02-07 eCollection Date: 2023-01-01 DOI: 10.1093/discim/kyad003

Katie J Smith, Giuseppe Sciumè, Shoba Amarnath

引用次数: 0

Diversification of immunoglobulin genes by gene conversion in the domestic chicken (Gallus gallus domesticus). 通过基因转化实现家鸡免疫球蛋白基因多样化

Discovery immunology Pub Date : 2023-01-19 eCollection Date: 2023-01-01 DOI: 10.1093/discim/kyad002

Jessica Mallaby, William Mwangi, Joseph Ng, Alexander Stewart, Daniel Dorey-Robinson, David Kipling, Uri Hershberg, Franca Fraternali, Venugopal Nair, Deborah Dunn-Walters

{"title":"Diversification of immunoglobulin genes by gene conversion in the domestic chicken (Gallus gallus domesticus).","authors":"Jessica Mallaby, William Mwangi, Joseph Ng, Alexander Stewart, Daniel Dorey-Robinson, David Kipling, Uri Hershberg, Franca Fraternali, Venugopal Nair, Deborah Dunn-Walters","doi":"10.1093/discim/kyad002","DOIUrl":"10.1093/discim/kyad002","url":null,"abstract":"Sustainable modern poultry production depends on effective protection against infectious diseases and a diverse range of antibodies is key for an effective immune response. In the domestic chicken, somatic gene conversion is the dominant process in which the antibody immunoglobulin genes are diversified. Affinity maturation by somatic hypermutation (SHM) also occurs, but the relative contribution of gene conversion versus somatic hypermutation to immunoglobulin (Ig) gene diversity is poorly understood. In this study, we use high throughput long-read sequencing to study immunoglobulin diversity in multiple immune-associated tissues in Rhode Island Red chickens. To better understand the impact of genetic diversification in the chicken, a novel gene conversion identification software was developed (BrepConvert). In this study, BrepConvert enabled the identification of over 1 million gene conversion events. Mapping the occurrence of putative somatic gene conversion (SGC) events throughout the variable gene region revealed repetitive and highly restricted patterns of genetic insertions in both the antibody heavy and light chains. These patterns coincided with the locations of genetic variability in available pseudogenes and align with antigen binding sites, predominately the complementary determining regions (CDRs). We found biased usage of pseudogenes during gene conversion, as well as immunoglobulin heavy chain diversity gene (IGHD) preferences during V(D)J gene rearrangement, suggesting that antibody diversification in chickens is more focused than the genetic potential for diversity would suggest.","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":"1 1","pages":"kyad002"},"PeriodicalIF":0.0,"publicationDate":"2023-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10917233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41469775","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

Protection from T cell-dependent colitis by the helminth-derived immunomodulatory mimic of transforming growth factor-β, Hp-TGM. 来自蠕虫的转化生长因子-β免疫调节模拟物Hp-TGM可防止T细胞依赖性结肠炎。

Discovery immunology Pub Date : 2023-01-18 eCollection Date: 2023-01-01 DOI: 10.1093/discim/kyad001

Danielle J Smyth, Madeleine P J White, Chris J C Johnston, Anne-Marie Donachie, Marta Campillo Poveda, Henry J McSorley, Rick M Maizels

{"title":"Protection from T cell-dependent colitis by the helminth-derived immunomodulatory mimic of transforming growth factor-β, Hp-TGM.","authors":"Danielle J Smyth, Madeleine P J White, Chris J C Johnston, Anne-Marie Donachie, Marta Campillo Poveda, Henry J McSorley, Rick M Maizels","doi":"10.1093/discim/kyad001","DOIUrl":"10.1093/discim/kyad001","url":null,"abstract":"In animal models of inflammatory colitis, pathology can be ameliorated by several intestinal helminth parasites, including the mouse nematode Heligmosomoides polygyrus. To identify parasite products that may exert anti-inflammatory effects in vivo, we tested H. polygyrus excretory-secretory (HES) products, as well as a recombinantly expressed parasite protein, transforming growth factor mimic (TGM), that functionally mimics the mammalian immunomodulatory cytokine TGF-β. HES and TGM showed a degree of protection in dextran sodium sulphate-induced colitis, with a reduction in inflammatory cytokines, but did not fully block the development of pathology. HES also showed little benefit in a similar acute trinitrobenzene sulphonic acid-induced model. However, in a T cell transfer-mediated model with recombination activation gene (RAG)-deficient mice, HES-reduced disease scores if administered throughout the first 2 or 4 weeks following transfer but was less effective if treatment was delayed until 14 days after T cell transfer. Recombinant TGM similarly dampened colitis in RAG-deficient recipients of effector T cells, and was effective even if introduced only once symptoms had begun to be manifest. These results are a promising indication that TGM may replicate, and even surpass, the modulatory properties of native parasite HES.","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":"2 1","pages":"kyad001"},"PeriodicalIF":0.0,"publicationDate":"2023-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9958376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9329589","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 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}

引用次数: 0