Journal of Leukocyte Biology最新文献

{"title":"Single-cell transcriptome analysis reveals atypical monocytes circulating ahead of acute graft-versus-host disease clinical onset.","authors":"Filipe Martins, Evarist Planet, Denis Marino, Marc Ansari, Didier Trono","doi":"10.1093/jleuko/qiae229","DOIUrl":"https://doi.org/10.1093/jleuko/qiae229","url":null,"abstract":"<p><p>Acute graft-versus-host disease (aGVHD) represents the rejection of the recipient's skin, gut, and liver tissues of an allogeneic hematopoietic stem cell transplantation (HSCT) by the donor T-cells. The onset of aGVHD is often rapid and its evolution is unpredictable. We undertook the single-cell RNA sequencing of peripheral blood mononuclear cells (PBMCs) collected before aGVHD clinical onset in three patients and from one patient afterward. We used four HSCT recipients who remained free of aGVHD as controls. This analysis unveiled the presence of particular subpopulations of circulating monocytes and cytotoxic T cells (CTLs) in pre-aGVHD samples up to 18 days before clinical disease. These pre-aGVHD monocytes were characterized by an upregulation of the M2 polarity marker CD163 and the transmembrane protein SIGLEC1/CD169. At the same time, their CTL counterparts stood out for the upregulation of the CXCL10 receptor CXCR3 and the antigenic stimulation marker CD70. The occurrence of CD163/SIGLEC1 co-expressing monocytes upstream of aGVHD onset was validated using transcriptomic data from an independent cohort and by flow cytometry in additional blood samples. These findings point to potential early diagnostic tools and preventive therapeutic strategies for aGVHD.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142467623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine learning algorithm approach to complete blood count can be used as early predictor of COVID-19 outcome.","authors":"Cecília Horta Ramalho-Pinto, Lucas Haniel de Araújo Ventura, Giovanna Caliman Camatta, Gabriela da Silveira-Nunes, Matheus de Souza Gomes, Hugo Itaru Sato, Murilo Soares Costa, Henrique Cerqueira Guimarães, Rafael Calvão Barbuto, Olindo Assis Martins Filho, Laurence Rodrigues do Amaral, Pedro Luiz Lima Bertarini, Santuza Maria Ribeiro Teixeira, Unaí Tupinambás, Andrea Teixeira Carvalho, Ana Maria Caetano Faria","doi":"10.1093/jleuko/qiae223","DOIUrl":"https://doi.org/10.1093/jleuko/qiae223","url":null,"abstract":"<p><p>Although the SARS-CoV-2 infection has established risk groups, identifying biomarkers for disease outcomes is still crucial to stratify patient risk and enhance clinical management. Optimal efficacy of COVID-19 antiviral medications relies on early administration within the initial five days of symptoms, assisting high-risk patients in avoiding hospitalization and improving survival chances. The complete blood count can be an efficient and affordable option to find biomarkers that predict the COVID-19 prognosis due to infection-induced alterations in various blood parameters. This study aimed to associate hematological parameters with different COVID-19 clinical forms and utilize them as disease outcome predictors. We performed a complete blood count in blood samples from 297 individuals with COVID-19 from Belo Horizonte, Brazil. Statistical analysis, as well as ROC Curves and machine learning Decision Tree algorithms were used to identify correlations, and their accuracy, between blood parameters and disease severity. In the initial four days of infection, traditional hematological COVID-19 alterations, such as lymphopenia, were not yet apparent. However, the monocyte percentage and granulocyte-to-lymphocyte ratio proved to be reliable predictors for hospitalization, even in cases where patients exhibited mild symptoms that later progressed to hospitalization. Thus, our findings demonstrate that COVID-19 patients with monocyte percentages lower than 7.7% and a granulocyte-to-lymphocyte ratio higher than 8.75 are assigned to the hospitalized group with a precision of 86%. This suggests that these variables can serve as important biomarkers in predicting disease outcomes and could be used to differentiate patients at hospital admission for managing therapeutic interventions, including early antiviral administration. Moreover, they are simple parameters that can be useful in minimally equipped health care units.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142467620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MerTK Signaling in Human Primary T cells Modulates Memory Potential and Improves Recall response.","authors":"Anne Rahbech, Annina Kurzay, Sara Fresnillo Saló, Tina Seremet, Reno Debets, Özcan Met, Marlies J W Peeters, Per Thor Straten","doi":"10.1093/jleuko/qiae226","DOIUrl":"10.1093/jleuko/qiae226","url":null,"abstract":"<p><p>Immune therapy using checkpoint inhibitors or adoptive cell transfer has revolutionized the treatment of several types of cancers. However, response to treatment is currently limited to a fraction of patients. Elucidation of immune modulatory mechanisms might optimize patient selection and present ways to modify anti-cancer immune responses. We recently discovered the expression and an important costimulatory role of TAM receptor MerTK signaling on activated human primary CD8+ T cells. Here we extend our study of the costimulatory role of MerTK expression in human CD8+ T cells. We uncover a clear link between MerTK expression and less differentiated Central Memory T cells based on an increased expression of CCR7, CD45RO, CD28, CD62L, and an altered metabolic profile. In addition, we observe an improved proliferative capacity and elevated expression of effector molecule IFNγ upon recall responses of MerTK-expressing cells in vitro. Finally, using gp100TCR-transduced T cells, we demonstrate how PROS1 treatment results in improved cytotoxicity and killing of tumors. Our findings describe a role of MerTK expression in T cells, which could be exploited in the search for improving immunotherapeutic approaches.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142467621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A new model measuring bacterial phagocytosis and phagolysosomal oxidisation in humans using the intradermal injection of methylene blue-labelled Escherichia coli.","authors":"George B Collins, Jhonatan de Souza Carvalho, Sandali C Jayasinghe, Urte Gumuliauskaite, David M Lowe, David C Thomas, Erik Årstad, Roel P H De Maeyer, Derek W Gilroy","doi":"10.1093/jleuko/qiae217","DOIUrl":"https://doi.org/10.1093/jleuko/qiae217","url":null,"abstract":"<p><p>Phagocytosis is an important leucocyte function, however using existing models it cannot be measured in human tissues in vivo. To address this, we characterized a new phagocytosis model using intradermal methylene blue-labelled Escherichia coli injection (MBEC). Methylene blue (MB) is a licensed human medicine and bacterial stain potentially useful for labelling E. coli that are safe for human injection. Ex vivo co-culture of leucocytes with MBEC caused MB to transfer into neutrophils and macrophages by phagocytosis. During this, a 'red shift' in MB fluorescence was shown to be caused by phagolysosomal oxidisation. Hence, MBEC co-culture could be used to measure phagocytosis and phagolysosomal oxidisation in humans, ex vivo. In healthy volunteers, inflammatory exudate sampling using suction blisters 2-24h after intradermal MBEC injection showed that tissue-acquired neutrophils and monocytes contained more MB than their circulating counterparts, whereas blood and inflamed tissue T, B and NK cells were MBlo. This was validated with spectral flow cytometry by visualizing the MB emission spectrum in tissue-acquired neutrophils. Neutrophil MB emission spectra demonstrated more 'red shift' at 24h compared to earlier time-points, in-keeping with progressive phagolysosomal MB oxidisation in neutrophils over time in vivo. This new MBEC model can therefore measure bacterial phagocytosis and phagolysosomal oxidisation in human skin, in vivo. This has a number of important research applications, for example in studying human phagocyte biology, testing novel antimicrobials, and understanding why certain groups such as males, the elderly or those with diabetes, recent surgery or malnutrition are at increased risk of bacterial infection.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142467618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polarization of the memory B cell response.","authors":"Lizzette Pérez-Pérez, Brian J Laidlaw","doi":"10.1093/jleuko/qiae228","DOIUrl":"https://doi.org/10.1093/jleuko/qiae228","url":null,"abstract":"<p><p>Memory B cells are long-lived cells that are induced following infection or vaccination. Upon antigen re-encounter, memory B cells rapidly differentiate into antibody-secreting or germinal center B cells. While memory B cells are an important component of long-term protective immunity following vaccination, they also contribute to the progression of diseases such as autoimmunity and allergy. Numerous subsets of memory B cells have been identified in mice and humans that possess important phenotypic and functional differences. Here, we review the transcriptional circuitry governing memory B cell differentiation and function. We then summarize emerging evidence that the inflammatory environment in which memory B cells develop has an important role in shaping their phenotype and examine the pathways regulating the development of memory B cells during a type 1-skewed and type-2 skewed immune response.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142467622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Protective Role of Transcription Factor Nrf2 in Murine Macrophage Activation Syndrome.","authors":"Paul M Gallo, Em Elliott, Grace C Ford, Chhanda Biswas, Jadyn M Wheaton, Jihwan Kim, Connie L Jiang, Niansheng Chu, Portia A Kreiger, Michele P Lambert, Edward M Behrens","doi":"10.1093/jleuko/qiae225","DOIUrl":"https://doi.org/10.1093/jleuko/qiae225","url":null,"abstract":"<p><strong>Objective: </strong>Macrophage activation syndrome (MAS) is characterized by multi-lineage cytopenias, hypercytokinemia, and tissue hemophagocytosis. Transcription factor Nrf2 is a master regulator of redox homeostasis. In this work we aim to investigate the role of Nrf2 in murine hyperinflammation and the mechanisms by which Nrf2 activation by red blood cell products regulates pro-inflammatory cytokine production.</p><p><strong>Methods: </strong>We induce murine MAS in wildtype and Nrf2 knockout (Nrf2 -/-) mice by repeat administration of TLR9-agonist CpG. Clinical and biochemical markers of disease were measured including complete blood counts, liver and spleen pathology, serum free heme, ferritin, and cytokine profiles. In vitro bone marrow derived macrophages and dendritic cells were used to investigate regulation of CpG-induced cytokine expression by oxidized red blood cells and hemin.</p><p><strong>Results: </strong>Patients with hyperinflammatory disease have higher levels of Nrf2 gene expression. Mice with CpG-induced hyperinflammation have elevated systemic lipid peroxidation which is exacerbated in Nrf2 -/- mice. Compared to wildtype controls, Nrf2 -/- mice develop significantly worse organomegaly, organ pathology, and reticulocytosis. Nrf2 -/- mice have exacerbated hypercytokinemia in cytokines central MAS physiology: IL-12, IFNg, and IL-10. In vitro we found that oxidized red blood cell lysates and hemin are able to suppress IL-12 transcription and protein production from bone marrow derived dendritic cells in a Nrf2-dependent manner.</p><p><strong>Conclusion: </strong>Together our findings show that transcription factor Nrf2 is highly expressed in patients with hyperinflammatory disease and demonstrate a protective role for Nrf2 in a murine model of MAS in part due to Nrf2-mediated suppression of proinflammatory cytokine production.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Miniaturized Isolation of Neutrophil Granules (MING) method allowed a deep proteome mapping of human neutrophil granules.","authors":"Gabrielly Alexandria, Hellen P Valerio, Mariana P Massafera, Lorenna R Reis, Fernando R Coelho, Paolo Di Mascio, Graziella E Ronsein","doi":"10.1093/jleuko/qiae224","DOIUrl":"https://doi.org/10.1093/jleuko/qiae224","url":null,"abstract":"<p><p>Neutrophils are the innate immune system's first line of defense, and their storage organelles are essential to their function. The storage organelles are divided into three different granule types named azurophilic, specific, and gelatinase granules, besides a fourth component called secretory vesicles. The isolation of neutrophil's granules is challenging, and the existing procedures rely on large sample volumes, about 400 mL of peripheral blood, precluding the use of multiple biological and technical replicates. Therefore, the aim of this study was to develop a miniaturized isolation of neutrophil granules (MING) method, using biochemical assays, mass spectrometry-based proteomics and a machine learning approach to investigate the protein content of these organelles. Neutrophils were isolated from 40 mL of blood collected from three apparently healthy volunteers and disrupted using nitrogen cavitation; the organelles were fractionated with a discontinuous 3-layer Percoll density gradient. The isolation was proven successful and allowed for a reasonable separation of neutrophil's storage organelles using a gradient approximately 37 times smaller than the methods described in the literature. Moreover, mass spectrometry-based proteomics identified 368 proteins in at least 3 of the 5 analyzed samples, and using a machine learning strategy aligned with markers from the literature, the localization of 50 proteins was predicted with confidence. When using markers determined within our dataset by a clusterization tool, the localization of 348 proteins was confidently determined. Importantly, this study was the first to investigate the proteome of neutrophil granules using technical and biological replicates, creating a reliable database for further studies.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neutrophil plasticity in liver diseases.","authors":"Jia Ming Nickolas Teo, Weixin Chen, Guang Sheng Ling","doi":"10.1093/jleuko/qiae222","DOIUrl":"https://doi.org/10.1093/jleuko/qiae222","url":null,"abstract":"<p><p>The liver has critical digestive, metabolic, and immunosurveillance roles, which get disrupted during liver diseases such as viral hepatitis, fatty liver disease, and hepatocellular carcinoma. While previous research on the pathological development of these diseases has focused on liver-resident immune populations, such as Kupffer cells, infiltrating immune cells responding to pathogens and disease also play crucial roles. Neutrophils are one such key population contributing to hepatic inflammation and disease progression. Belonging to the initial waves of immune response to threats, neutrophils suppress bacterial and viral spread during acute infections, and have homeostasis-restoring functions. Whereas during chronic insults, they display their plastic nature by responding to the inflammatory environment and develop new phenotypes alongside longer lifespans. This review summarizes the diversity in neutrophil function and subpopulations present at steady state, during liver disease, and during liver cancer.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"B-cell Interleukin 1 Receptor 1 (IL1R1) modulates the female adipose tissue immune microenvironment during aging.","authors":"Anna Carey, Louise E Pitcher, In Hwa Jang, Katie Nguyen, Stephanie Cholensky, Paul D Robbins, Christina D Camell","doi":"10.1093/jleuko/qiae219","DOIUrl":"https://doi.org/10.1093/jleuko/qiae219","url":null,"abstract":"<p><p>Myeloid cell production of interleukin-1β (IL-1β) drives inflammaging in visceral adipose tissue (vWAT) and contributes to the expansion of interleukin-1 receptor 1 (Il1r1) positive aged adipose B-cells (AABs). AABs promote metabolic dysfunction and inflammation under inflammatory challenges. However, it is unclear whether IL-1β contributes to AAB-associated inflammation during aging. Using a B-cell specific knockout of Il1r1 (BKO mice), we characterized old vWAT in the absence of IL-1β - B-cell signaling. In addition to sex-specific metabolic improvements in females, we identified a reduction in the proportion of B-cells and a sex-specific increase in the B1:B2 B-cell ratio in BKO vWAT. Using single cell RNA-sequencing of vWAT immune cells, we observed that BKO differentially affected inflammatory signaling in vWAT immune cells. These data suggest that IL-1β - B-cell signaling supports the inflammatory response in multiple cell types and provides insight into the complex microenvironment in aged vWAT.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thymic stromal lymphopoietin signaling in B cells from progenitors to plasma cells.","authors":"Phillip P Domeier, Steven F Ziegler","doi":"10.1093/jleuko/qiae216","DOIUrl":"https://doi.org/10.1093/jleuko/qiae216","url":null,"abstract":"<p><p>Thymic stromal lymphopoietin (TSLP) is an established pleotropic alarmin cytokine that is generated at barrier tissues to induce type 2 immune responses, but its role in regulating the diversity of B cells is poorly understood. Here, we will highlight the key findings that underpin our limited understanding of the role TSLP in modulating different stages of B cell development. We will also provide an overview of how TSLP drives B cell-mediated immune disease and how novel TSLP-blocking biologics could be used to modulate B cell responses. TSLP is critical for the regulation, diversity, and longevity of humoral immunity.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}