Discovery immunology最新文献_第2页

The ontogenesis and heterogeneity of basophils 嗜碱性粒细胞的本体形成和异质性

Discovery immunology Pub Date : 2024-02-02 DOI: 10.1093/discim/kyae003

Jiyeon Park, Suk-Jo Kang

{"title":"The ontogenesis and heterogeneity of basophils","authors":"Jiyeon Park, Suk-Jo Kang","doi":"10.1093/discim/kyae003","DOIUrl":"https://doi.org/10.1093/discim/kyae003","url":null,"abstract":"\u0000 Basophils are the rarest leukocytes, but they have essential roles in protection against helminths, allergic disorders, autoimmune diseases, and some cancers. For years, the clinical significance of basophils has been neglected because of the lack of proper experimental tools to study them. The development of basophil-specific antibodies and animal models, along with genomic advances like single-cell transcriptomics, has greatly enhanced our understanding of basophil biology. Recent discoveries regarding basophils prompted us to write this review, emphasizing the basophil developmental pathway. In it, we chronologically examine the steps of basophil development in various species, which reveals the apparent advent of basophils predating IgE and basophil’s IgE-independent regulatory role in primitive vertebrates. Then, we cover studies of basophil development in adult bone marrow, and compare those of murine and human basophils, introducing newly identified basophil progenitors and mature basophil subsets, as well as the transcription factors that regulate the transitions between them. Last, we discuss the heterogeneity of tissue-resident basophils, which may develop through extramedullary hematopoiesis. We expect that this review will contribute to a deeper understanding of basophil biology from the intricate aspects of basophil development and differentiation, offering valuable insights for both researchers and clinicians.","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139809575","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 ontogenesis and heterogeneity of basophils 嗜碱性粒细胞的本体形成和异质性

Discovery immunology Pub Date : 2024-02-02 DOI: 10.1093/discim/kyae003

Jiyeon Park, Suk-Jo Kang

{"title":"The ontogenesis and heterogeneity of basophils","authors":"Jiyeon Park, Suk-Jo Kang","doi":"10.1093/discim/kyae003","DOIUrl":"https://doi.org/10.1093/discim/kyae003","url":null,"abstract":"\u0000 Basophils are the rarest leukocytes, but they have essential roles in protection against helminths, allergic disorders, autoimmune diseases, and some cancers. For years, the clinical significance of basophils has been neglected because of the lack of proper experimental tools to study them. The development of basophil-specific antibodies and animal models, along with genomic advances like single-cell transcriptomics, has greatly enhanced our understanding of basophil biology. Recent discoveries regarding basophils prompted us to write this review, emphasizing the basophil developmental pathway. In it, we chronologically examine the steps of basophil development in various species, which reveals the apparent advent of basophils predating IgE and basophil’s IgE-independent regulatory role in primitive vertebrates. Then, we cover studies of basophil development in adult bone marrow, and compare those of murine and human basophils, introducing newly identified basophil progenitors and mature basophil subsets, as well as the transcription factors that regulate the transitions between them. Last, we discuss the heterogeneity of tissue-resident basophils, which may develop through extramedullary hematopoiesis. We expect that this review will contribute to a deeper understanding of basophil biology from the intricate aspects of basophil development and differentiation, offering valuable insights for both researchers and clinicians.","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139869558","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

Signalling mechanisms driving homeostatic and inflammatory effects of interleukin-15 on tissue lymphocytes. 驱动白细胞介素-15 对组织淋巴细胞产生平衡和炎症效应的信号机制。

Discovery immunology Pub Date : 2024-01-30 eCollection Date: 2024-01-01 DOI: 10.1093/discim/kyae002

Neema Skariah, Olivia J James, Mahima Swamy

{"title":"Signalling mechanisms driving homeostatic and inflammatory effects of interleukin-15 on tissue lymphocytes.","authors":"Neema Skariah, Olivia J James, Mahima Swamy","doi":"10.1093/discim/kyae002","DOIUrl":"10.1093/discim/kyae002","url":null,"abstract":"There is an intriguing dichotomy in the function of cytokine interleukin-15-at low levels, it is required for the homeostasis of the immune system, yet when it is upregulated in response to pathogenic infections or in autoimmunity, IL-15 drives inflammation. IL-15 associates with the IL-15Rα within both myeloid and non-haematopoietic cells, where IL-15Rα trans-presents IL-15 in a membrane-bound form to neighboring cells. Alongside homeostatic maintenance of select lymphocyte populations such as NK cells and tissue-resident T cells, when upregulated, IL-15 also promotes inflammatory outcomes by driving effector function and cytotoxicity in NK cells and T cells. As chronic over-expression of IL-15 can lead to autoimmunity, IL-15 expression is tightly regulated. Thus, blocking dysregulated IL-15 and its downstream signalling pathways are avenues for immunotherapy. In this review we discuss the molecular pathways involved in IL-15 signalling and how these pathways contribute to both homeostatic and inflammatory functions in IL-15-dependent mature lymphoid populations, focusing on innate, and innate-like lymphocytes in tissues.","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10883678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139974799","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

Deciphering the relationship between temperature and immunity 解读温度与免疫力之间的关系

Discovery immunology Pub Date : 2024-01-30 DOI: 10.1093/discim/kyae001

Elizabeth Maloney, Darragh Duffy

{"title":"Deciphering the relationship between temperature and immunity","authors":"Elizabeth Maloney, Darragh Duffy","doi":"10.1093/discim/kyae001","DOIUrl":"https://doi.org/10.1093/discim/kyae001","url":null,"abstract":"Summary Fever is a hallmark symptom of disease across the animal kingdom. Yet, despite the evidence linking temperature fluctuation and immune response, much remains to be discovered about the molecular mechanisms governing these interactions. In patients with rheumatoid arthritis, for instance, it is clinically accepted that joint temperature can predict disease progression. But it was only recently demonstrated that the mitochondria of stimulated T cells can rise to an extreme 50°C, potentially indicating a cellular source of these localized ‘fevers’. A challenge to dissecting these mechanisms is a bidirectional interplay between temperature and immunity. Heat shock response is found in virtually all organisms, activating protective pathways when cells are exposed to elevated temperatures. However, the temperature threshold that activates these pathways can vary within the same organism, with human immune cells, in particular, demonstrating differential sensitivity to heat. Such inter-cellular variation may be clinically relevant given the small but significant temperature differences seen between tissues, ages, and sexes. Greater understanding of how such small temperature perturbations mediate immune responses may provide new explanations for persistent questions in disease such as sex disparity in disease prevalence. Notably, the prevalence and severity of many maladies are rising with climate change, suggesting temperature fluctuations can interact with disease on multiple levels. As global temperatures are rising, and our body temperatures are falling, questions regarding temperature–immune interactions are increasingly critical. Here, we review this aspect of environmental interplay to better understand temperature’s role in immune variation and subsequent risk of disease.","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140480783","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 effect of abatacept on T cell activation is not long-lived in vivo 阿帕他赛对体内 T 细胞活化的影响并不持久

Discovery immunology Pub Date : 2024-01-04 DOI: 10.1093/discim/kyad029

Larissa C da Rosa, H. Scales, R. Benson, James M Brewer, Iain B. McInnes, P. Garside

引用次数: 0

Optimising a linear ‘Doggybone’ DNA vaccine for influenza virus through the incorporation of DNA targeting sequences and neuraminidase antigen 通过加入 DNA 靶向序列和神经氨酸酶抗原优化流感病毒线性 "Doggybone "DNA 疫苗

Discovery immunology Pub Date : 2024-01-03 DOI: 10.1093/discim/kyad030

Robert F. Cunliffe, David C. Stirling, Ilaria Razzano, Valarmathy Murugaiah, E. Montomoli, Sungwon Kim, Madina Wane, Helen Horton, Lisa J. Caproni, J. Tregoning

{"title":"Optimising a linear ‘Doggybone’ DNA vaccine for influenza virus through the incorporation of DNA targeting sequences and neuraminidase antigen","authors":"Robert F. Cunliffe, David C. Stirling, Ilaria Razzano, Valarmathy Murugaiah, E. Montomoli, Sungwon Kim, Madina Wane, Helen Horton, Lisa J. Caproni, J. Tregoning","doi":"10.1093/discim/kyad030","DOIUrl":"https://doi.org/10.1093/discim/kyad030","url":null,"abstract":"\u0000 Influenza virus represents a challenge for traditional vaccine approaches due to its seasonal changes and potential for zoonotic transmission. Nucleic acid vaccines can overcome some of these challenges, especially through the inclusion of multiple antigens to increase breadth of response. RNA vaccines were an important part of the response to the COVID-19 pandemic, but for future outbreaks DNA vaccines may have some advantages in terms of stability and manufacturing cost that warrant continuing investigation to fully realise their potential. Here we investigate influenza virus vaccines made using a closed loop linear DNA platform, Doggybone™ DNA (dbDNA), produced by a rapid and scalable cell-free method. Influenza vaccines have mostly focussed on Haemagglutinin (HA), but the inclusion of Neuraminidase (NA) may provide additional protection. Here we explored the potential of including NA in a dbDNA vaccine, looking at DNA optimisation, mechanism and breadth of protection. We showed that DNA targeting sequences (DTS) improved immune responses against HA but not NA. We explored whether NA vaccine induced protection against influenza virus infection was cell mediated but depletion of CD8 and NK cells made no impact, suggesting it was antibody mediated. This is reflected in restriction of protection only homologous strains of influenza virus. Importantly, we saw that including both HA and NA in a single combined vaccine did not dampen the immune response to either one. Overall, we show that linear dbDNA can induce an immune response against NA which may offer increased protection in instances of HA mismatch where NA remains more conserved.","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139389539","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

Rab46: a novel player in mast cell function. Rab46：肥大细胞功能的新参与者。

Discovery immunology Pub Date : 2023-12-22 eCollection Date: 2024-01-01 DOI: 10.1093/discim/kyad028

Lucia Pedicini, Jessica Smith, Sinisa Savic, Lynn McKeown

{"title":"Rab46: a novel player in mast cell function.","authors":"Lucia Pedicini, Jessica Smith, Sinisa Savic, Lynn McKeown","doi":"10.1093/discim/kyad028","DOIUrl":"https://doi.org/10.1093/discim/kyad028","url":null,"abstract":"Mast cells are infamous for mediating allergic and inflammatory diseases due to their capacity of rapidly releasing a wide range of inflammatory mediators stored in cytoplasmic granules. However, mast cells also have several important physiological roles that involve selective and agonist-specific release of these active mediators. While a filtering mechanism at the plasma membrane could regulate the selective release of some cargo, the plethora of stored cargo and the diversity of mast cell functions suggests the existence of granule subtypes with distinct trafficking pathways. The molecular mechanisms underlying differential trafficking and exocytosis of these granules are not known, neither is it clear how granule trafficking is coupled to the stimulus. In endothelial cells, a Rab GTPase, Rab46, responds to histamine but not thrombin signals, and this regulates the trafficking of a subpopulation of endothelial-specific granules. Here, we sought to explore, for the first time, if Rab46 plays a role in mast cell function. We demonstrate that Rab46 is highly expressed in human and murine mast cells, and Rab46 genetic deletion has an effect on mast cell degranulation that depends on both stimuli and mast cell subtype. This initial insight into the contribution of Rab46 to mast cell function and the understanding of the role of Rab46 in stimuli-dependent trafficking in other cell types necessitates further investigations of Rab46 in mast cell granular trafficking so that novel and specific therapeutic targets for treatment of the diverse pathologies mediated by mast cells can be developed.","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10917158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140860771","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 glucocorticoid dexamethasone inhibits HIF-1α stabilization and metabolic reprogramming in lipopolysaccharide-stimulated primary macrophages. 糖皮质激素地塞米松抑制脂多糖刺激的原代巨噬细胞中HIF-1α的稳定和代谢重编程。

Discovery immunology Pub Date : 2023-12-04 eCollection Date: 2023-01-01 DOI: 10.1093/discim/kyad027

Sally A Clayton, Chloe Lockwood, John D O'Neil, Kalbinder K Daley, Sofia Hain, Dina Abdelmottaleb, Oliwia O Bolimowska, Daniel A Tennant, Andrew R Clark

{"title":"The glucocorticoid dexamethasone inhibits HIF-1α stabilization and metabolic reprogramming in lipopolysaccharide-stimulated primary macrophages.","authors":"Sally A Clayton, Chloe Lockwood, John D O'Neil, Kalbinder K Daley, Sofia Hain, Dina Abdelmottaleb, Oliwia O Bolimowska, Daniel A Tennant, Andrew R Clark","doi":"10.1093/discim/kyad027","DOIUrl":"10.1093/discim/kyad027","url":null,"abstract":"Synthetic glucocorticoids are used to treat many chronic and acute inflammatory conditions. Frequent adverse effects of prolonged exposure to glucocorticoids include disturbances of glucose homeostasis caused by changes in glucose traffic and metabolism in muscle, liver, and adipose tissues. Macrophages are important targets for the anti-inflammatory actions of glucocorticoids. These cells rely on aerobic glycolysis to support various pro-inflammatory and antimicrobial functions. Employing a potent pro-inflammatory stimulus in two commonly used model systems (mouse bone marrow-derived and human monocyte-derived macrophages), we showed that the synthetic glucocorticoid dexamethasone inhibited lipopolysaccharide-mediated activation of the hypoxia-inducible transcription factor HIF-1α, a critical driver of glycolysis. In both cell types, dexamethasone-mediated inhibition of HIF-1α reduced the expression of the glucose transporter GLUT1, which imports glucose to fuel aerobic glycolysis. Aside from this conserved response, other metabolic effects of lipopolysaccharide and dexamethasone differed between human and mouse macrophages. These findings suggest that glucocorticoids exert anti-inflammatory effects by impairing HIF-1α-dependent glucose uptake in activated macrophages. Furthermore, harmful and beneficial (anti-inflammatory) effects of glucocorticoids may have a shared mechanistic basis, depending on the alteration of glucose utilization.","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10917182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140861773","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 generation of senescent-like CD4+ EMRA T cells in T2D and their contribution to poor COVID-19 vaccine responses T2D 中衰老样 CD4+ EMRA T 细胞的生成及其对 COVID-19 疫苗应答不良的贡献

Discovery immunology Pub Date : 2023-11-28 DOI: 10.1093/discim/kyad026

C. Garrod-Ketchley, Laure Mourgue d'Algue, Katie Littlewood, Gillian Hood, Anne Worthington, Melanie Pattrick, Caroline Sutcliffe, Zoi Valla, Noorshad Joti, Udeshi Zalak, Amy Edwards, Sarah Finer, S. Henson

{"title":"The generation of senescent-like CD4+ EMRA T cells in T2D and their contribution to poor COVID-19 vaccine responses","authors":"C. Garrod-Ketchley, Laure Mourgue d'Algue, Katie Littlewood, Gillian Hood, Anne Worthington, Melanie Pattrick, Caroline Sutcliffe, Zoi Valla, Noorshad Joti, Udeshi Zalak, Amy Edwards, Sarah Finer, S. Henson","doi":"10.1093/discim/kyad026","DOIUrl":"https://doi.org/10.1093/discim/kyad026","url":null,"abstract":"CD4+ T cells are essential for protection from viral pathogens, such as SARS-CoV-2. However, an increase in the dysfunction CD4+ EMRA subset is likely to hinder the immune response towards viruses. We show here that CD4+ EMRAs are increased with elevated blood glucose, such as people living with T2D, which alters mitochondrial function and causes the differentiation of CD4+ T cells, reducing the immune response to COVID-19 vaccination. CD4+ T cells were examined for senescence, their insulin dynamics, and mitochondrial function after in vitro culture of high and low glucose media, with or without rotenone or mitoQ. Serum samples were used to assess circulating inflammation and IgG antibodies to SARS-CoV-2. People living with T2D had increased expression of CD4+ EMRA T cells, the appearance of which correlated with increasing blood glucose values. The T2D cohort showed a reduced mitochondrial membrane potential and increased mtROS production. These results were mimicked using high glucose media which accelerated CD4+ T cell differentiation and reduced MMP. People living with T2D (non-hyperglycaemic and hyperglycaemic) had altered expression of inflammatory mediators. CD4+ EMRA cells did not respond to COVID-19 peptides, and people with T2D had a reduced T cell and antibody response to SARS-CoV-2 S1 spike protein. We have shown that senescent-like CD4+ EMRA influence the viral response in SARS-CoV-2 and that CD4+ EMRAs may arise from faulty mitochondrial dynamics due to increased environmental glucose. Further study is required to determine the direct link increased glucose has with CD4+ EMRA formation.","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139216519","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

T cell and bacterial microbiota interaction at intestinal and skin epithelial interfaces 肠道和皮肤上皮界面的 T 细胞与细菌微生物群相互作用

Discovery immunology Pub Date : 2023-11-25 DOI: 10.1093/discim/kyad024

Damian Maseda, S. Manfredo-Vieira, Aimee S Payne

引用次数: 0