European Journal of Immunology最新文献_第5页

Testosterone and estradiol reduce inflammation of human macrophages induced by anti-SARS-CoV-2 IgG. 睾酮和雌二醇可减少抗 SARS-CoV-2 IgG 诱导的人类巨噬细胞炎症。

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-09-09 DOI: 10.1002/eji.202451226

Sona Allahverdiyeva, Chiara E Geyer, Jennifer Veth, Laura M de Vries, Steven W de Taeye, Marit J van Gils, Jeroen den Dunnen, Hung-Jen Chen

{"title":"Testosterone and estradiol reduce inflammation of human macrophages induced by anti-SARS-CoV-2 IgG.","authors":"Sona Allahverdiyeva, Chiara E Geyer, Jennifer Veth, Laura M de Vries, Steven W de Taeye, Marit J van Gils, Jeroen den Dunnen, Hung-Jen Chen","doi":"10.1002/eji.202451226","DOIUrl":"https://doi.org/10.1002/eji.202451226","url":null,"abstract":"COVID-19, the disease caused by SARS-CoV-2, particularly causes severe inflammatory disease in elderly, obese, and male patients. Since both aging and obesity are associated with decreased testosterone and estradiol expression, we hypothesized that decreased hormone levels contribute to excessive inflammation in the context of COVID-19. Previously, we and others have shown that hyperinflammation in severe COVID-19 patients is induced by the production of pathogenic anti-spike IgG antibodies that activate alveolar macrophages. Therefore, we developed an in vitro assay in which we stimulated human macrophages with viral stimuli, anti-spike IgG immune complexes, and different sex hormones. Treatment with levels of testosterone reflecting young adults led to a significant reduction in TNF and IFN-γ production by human macrophages. In addition, estradiol significantly attenuated the production of a very broad panel of cytokines, including TNF, IL-1β, IL-6, IL-10, and IFN-γ. Both testosterone and estradiol reduced the expression of Fc gamma receptors IIa and III, the two main receptors responsible for anti-spike IgG-induced inflammation. Combined, these findings indicate that sex hormones reduce the inflammatory response of human alveolar macrophages to specific COVID-19-associated stimuli, thereby providing a potential immunological mechanism for the development of severe COVID-19 in both older male and female patients.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e2451226"},"PeriodicalIF":4.5,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142152715","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}

引用次数: 0

ThymoSpheres culture: A model to study human polyclonal unconventional T cells. 胸腺球培养：研究人类多克隆非常规 T 细胞的模型。

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-09-09 DOI: 10.1002/eji.202451265

Lore Billiet, Hanne Jansen, Melissa Pille, Lena Boehme, Guillem Sanchez Sanchez, Laurenz De Cock, Glenn Goetgeluk, Eva Pascal, Stijn De Munter, Lucas Deseins, Joline Ingels, Thomas Michiels, Robrecht De Vos, Amin Zolfaghari, Niels Vandamme, Jana Roels, Tessa Kerre, Ruslan I Dmitriev, Tom Taghon, David Vermijlen, Bart Vandekerckhove

{"title":"ThymoSpheres culture: A model to study human polyclonal unconventional T cells.","authors":"Lore Billiet, Hanne Jansen, Melissa Pille, Lena Boehme, Guillem Sanchez Sanchez, Laurenz De Cock, Glenn Goetgeluk, Eva Pascal, Stijn De Munter, Lucas Deseins, Joline Ingels, Thomas Michiels, Robrecht De Vos, Amin Zolfaghari, Niels Vandamme, Jana Roels, Tessa Kerre, Ruslan I Dmitriev, Tom Taghon, David Vermijlen, Bart Vandekerckhove","doi":"10.1002/eji.202451265","DOIUrl":"https://doi.org/10.1002/eji.202451265","url":null,"abstract":"In vitro cultures remain crucial for studying the fundamental mechanisms of human T-cell development. Here, we introduce a novel in vitro cultivation system based on ThymoSpheres (TS): dense spheroids consisting of DLL4-expressing stromal cells and human hematopoietic precursor cells, in the absence of thymic epithelial cells. These spheroids are subsequently cultured at the air-liquid interphase. TS generate large numbers of mature T cells, are easy to manipulate, scalable, and can be repeatably sampled to monitor T-cell differentiation. The mature T cells generated from primary human hematopoietic precursor cells were extensively characterized using single-cell RNA and combined T-cell receptor (TCR) sequencing. These predominantly CD8α T cells exhibit transcriptional and TCR CDR3 characteristics similar to the recently described human polyclonal αβ unconventional T cell (UTC) lineage. This includes the expression of hallmark genes associated with agonist selection, such as IKZF2 (Helios), and the expression of various natural killer receptors. The TCR repertoire of these UTCs is polyclonal and enriched for CDR3-associated autoreactive features and early rearrangements of the TCR-α chain. In conclusion, TS cultures offer an intriguing platform to study the development of this human polyclonal UTC lineage and its inducing selection mechanisms.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e2451265"},"PeriodicalIF":4.5,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142152716","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}

引用次数: 0

MicroRNA-146a deficiency enhances host protection against murine cytomegalovirus. 微RNA-146a缺乏可增强宿主对小鼠巨细胞病毒的保护。

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-09-09 DOI: 10.1002/eji.202451173

Pamela Wong, Jeffrey W Leong, Hyogon Sohn, Lily Chang, Catherine R Keppel, Carly C Neal, Celia C Cubitt, Tony Yao, Molly P Keppel, Jennifer Tran, Allison Burdi, Kimberly Hwang, Leslie A Fogel, Timothy Schappe, Lynne Marsala, Melissa M Berrien-Elliott, Julia A Wagner, Stephanie E Schneider, Ryan P Sullivan, Jeanette T Pingel, Megan A Cooper, Anthony R French, Todd A Fehniger

{"title":"MicroRNA-146a deficiency enhances host protection against murine cytomegalovirus.","authors":"Pamela Wong, Jeffrey W Leong, Hyogon Sohn, Lily Chang, Catherine R Keppel, Carly C Neal, Celia C Cubitt, Tony Yao, Molly P Keppel, Jennifer Tran, Allison Burdi, Kimberly Hwang, Leslie A Fogel, Timothy Schappe, Lynne Marsala, Melissa M Berrien-Elliott, Julia A Wagner, Stephanie E Schneider, Ryan P Sullivan, Jeanette T Pingel, Megan A Cooper, Anthony R French, Todd A Fehniger","doi":"10.1002/eji.202451173","DOIUrl":"https://doi.org/10.1002/eji.202451173","url":null,"abstract":"Natural killer (NK) cells are innate lymphoid cells that protect a host from viral infections and malignancies. MicroRNA-146a (miR-146a) is an important regulator of immune function that is highly expressed in NK cells and is further upregulated during murine cytomegalovirus (MCMV) infection. Here we utilized mice with a global targeted deletion of miR-146a to understand its impact on the innate immune responses to MCMV infection. MiR-146a-/- mice were protected from lethal MCMV infection, which was intrinsic to the hematopoietic compartment based on bone marrow chimera experiments. NK cell depletion abrogated this protection, implicating NK cells as critical for the miR-146a-/- protection from MCMV. Surprisingly, NK cells from miR-146a-deficient mice were largely similar to control NK cells with respect to development, maturation, trafficking, and effector functions. However, miR-146a-/- mice had increased NK cell numbers and frequency of the most mature Stage IV (CD27-CD11b+) NK cells in the liver at baseline, enhanced STAT1 phosphorylation, and increased selective expansion of Ly49H+ NK cells and T cells during MCMV infection. This study demonstrates a critical role for miR-146a in the host response to MCMV, arising from mechanisms that include increased NK cell numbers and early T-cell expansion.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e2451173"},"PeriodicalIF":4.5,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142152714","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}

引用次数: 0

Key actors in neuropathophysiology: The role of γδ T cells. 神经病理生理学中的关键角色：γδ T 细胞的作用

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-09-06 DOI: 10.1002/eji.202451055

Deniz Bulgur, Raquel Macedo Moura, Julie C Ribot

{"title":"Key actors in neuropathophysiology: The role of γδ T cells.","authors":"Deniz Bulgur, Raquel Macedo Moura, Julie C Ribot","doi":"10.1002/eji.202451055","DOIUrl":"https://doi.org/10.1002/eji.202451055","url":null,"abstract":"The neuroimmune axis has been the focus of many studies, with special emphasis on the interactions between the central nervous system and the different immune cell subsets. T cells are namely recognized to play a critical role due to their interaction with nerves, by secreting cytokines and neurotrophins, which regulate the development, function, and survival of neurons. In this context, γδ T cells are particularly relevant, as they colonize specific tissues, namely the meninges, and have a wide variety of complex functions that balance physiological systems. Notably, γδ T cells are not only key components for maintaining brain homeostasis but are also responsible for triggering or preventing inflammatory responses in various pathologies, including neurodegenerative diseases as well as neuropsychiatric and developmental disorders. Here, we provide an overview of the current state of the art on the contribution of γδ T cells in neuropathophysiology and delve into the molecular mechanisms behind it. We aim to shed light on γδ T cell functions in the central nervous system while highlighting upcoming challenges in the field and providing new clues for potential therapeutic strategies.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e2451055"},"PeriodicalIF":4.5,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142138779","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}

引用次数: 0

Bead-by-bead normalization of single antigen assays: A necessary step for accurate detection of weak anti-HLA antibodies 单抗原检测的逐珠归一化：准确检测弱抗 HLA 抗体的必要步骤。

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-09-05 DOI: 10.1002/eji.202451181

Cédric Usureau, Romain Lhotte, Magali Devriese, Jérémy Siemowski, Lionel Gabet, Véronique Letort, Jean-Luc Taupin

{"title":"Bead-by-bead normalization of single antigen assays: A necessary step for accurate detection of weak anti-HLA antibodies","authors":"Cédric Usureau, Romain Lhotte, Magali Devriese, Jérémy Siemowski, Lionel Gabet, Véronique Letort, Jean-Luc Taupin","doi":"10.1002/eji.202451181","DOIUrl":"10.1002/eji.202451181","url":null,"abstract":"Ascertaining the presence of weakly positive anti-HLA donor-specific antibodies (DSA) in organ transplantation with multiplex single antigen beads assays may be challenging despite their high sensitivity due to technical variability issues. Through extensive datasets of Next-Generation Sequencing HLA typings and single antigen analyses, we reassessed the mean fluorescence intensity (MFI) positivity threshold of the assay to enhance accuracy. By showing that some beads were more prone to false positivity than others, we propose a nuanced approach that accounts for nonspecific intrinsic reactivities at the HLA antigen level, that is, on a bead-by-bead basis, as it enhances assay precision and reliability. This is substantiated by a comprehensive statistical analysis of MFI values and the implementation of the determination of a “Quantile Adjusted Threshold 500” (QAT500) value for each bead. Applied to DSA detection during patients’ follow-up, this approach discriminated better and earlier low-strength DSA that would later raise their MFI above the clinically relevant threshold of 3000. Moving from a subjective interpretation to a more objective and precise methodology allows for standardizing HLA antibody and DSA detection. The study emphasizes the need for further research with real clinical data to validate and refine this approach.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"54 11","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202451181","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tviblindi algorithm identifies branching developmental trajectories of human B-cell development and describes abnormalities in RAG-1 and WAS patients. Tviblindi 算法识别了人类 B 细胞发育的分支发育轨迹，并描述了 RAG-1 和 WAS 患者的异常情况。

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-09-05 DOI: 10.1002/eji.202451004

Marina Bakardjieva, Ondřej Pelák, Marjolein Wentink, Hana Glier, David Novák, Jitka Stančíková, Daniela Kužílková, Ester Mejstříková, Iga Janowska, Marta Rizzi, Mirjam van der Burg, Jan Stuchlý, Tomáš Kalina

{"title":"Tviblindi algorithm identifies branching developmental trajectories of human B-cell development and describes abnormalities in RAG-1 and WAS patients.","authors":"Marina Bakardjieva, Ondřej Pelák, Marjolein Wentink, Hana Glier, David Novák, Jitka Stančíková, Daniela Kužílková, Ester Mejstříková, Iga Janowska, Marta Rizzi, Mirjam van der Burg, Jan Stuchlý, Tomáš Kalina","doi":"10.1002/eji.202451004","DOIUrl":"https://doi.org/10.1002/eji.202451004","url":null,"abstract":"Detailed knowledge of human B-cell development is crucial for the proper interpretation of inborn errors of immunity and malignant diseases. It is of interest to understand the kinetics of protein expression changes during development, but also to properly interpret the major and possibly alternative developmental trajectories. We have investigated human samples from healthy individuals with the aim of describing all B-cell developmental trajectories. We validated a 30-parameter mass cytometry panel and demonstrated the utility of \"vaevictis\" visualization of B-cell developmental stages. We used the trajectory inference tool \"tviblindi\" to exhaustively describe all trajectories leading to all developmental ends discovered in the data. Focusing on Natural Effector B cells, we demonstrated the dynamics of expression of nuclear factors (PAX-5, TdT, Ki-67, Bcl-2), cytokine and chemokine receptors (CD127, CXCR4, CXCR5) in relation to the canonical B-cell developmental stage markers. We observed branching of the memory development, where follicular memory formation was marked by CD73 expression. Lastly, we performed an analysis of two example cases of abnormal B-cell development caused by mutations in RAG-1 and Wiskott-Aldrich syndrome gene in patients with primary immunodeficiency. In conclusion, we developed, validated, and presented a comprehensive set of tools for the investigation of B-cell development in the bone marrow compartment.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e2451004"},"PeriodicalIF":4.5,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131388","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}

引用次数: 0

Innate T-cell-derived IL-17A/F protects from bleomycin-induced acute lung injury but not bleomycin or adenoviral TGF-β1-induced lung fibrosis in mice. 先天性 T 细胞衍生的 IL-17A/F 可保护小鼠免受博莱霉素诱导的急性肺损伤，但不能保护小鼠免受博莱霉素或腺病毒 TGF-β1 诱导的肺纤维化。

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-09-05 DOI: 10.1002/eji.202451323

Marie T Moog, Melina Baltes, Tina Röpke, Franziska Aschenbrenner, Regina Maus, Jennifer Stolper, Danny Jonigk, Immo Prinz, Martin Kolb, Ulrich A Maus

{"title":"Innate T-cell-derived IL-17A/F protects from bleomycin-induced acute lung injury but not bleomycin or adenoviral TGF-β1-induced lung fibrosis in mice.","authors":"Marie T Moog, Melina Baltes, Tina Röpke, Franziska Aschenbrenner, Regina Maus, Jennifer Stolper, Danny Jonigk, Immo Prinz, Martin Kolb, Ulrich A Maus","doi":"10.1002/eji.202451323","DOIUrl":"https://doi.org/10.1002/eji.202451323","url":null,"abstract":"The pathobiology of IL-17 in lung fibrogenesis is controversial. Here we examined the role of IL-17A/F in bleomycin (BLM) and adenoviral TGF-β1-induced lung fibrosis in mice. In both experimental models, WT and IL17af-/- mice showed increased collagen contents and remodeled lung architecture as assessed by histopathological examination, suggesting that IL-17A/F is dispensable for lung fibrogenesis. However, IL17af-/- mice responded to the BLM challenge with perturbed lung leukocyte subset recruitment. More specifically, bleomycin triggered angiocentric neutrophilic infiltrations of the lung accompanied by increased mortality of IL17af-/- but not WT mice. WT bone marrow transplantation failed to correct this phenotype in BLM-challenged IL17af-/- mice. Conversely, IL17a/f-/- bone marrow transplantation → WT did not perturb lung leukocytic responses upon BLM. At the same time, IL17af-/- mice treated with recombinant IL-17A/F showed an attenuated lung inflammatory response to BLM. Together, the data show that the degree of BLM-driven acute lung injury was critically dependent on the presence of IL-17A/F, while in both models, the fibrotic remodeling process was not.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":" ","pages":"e2451323"},"PeriodicalIF":4.5,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131360","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}

引用次数: 0

Antibody density on bacteria regulates C1q recruitment by monoclonal IgG but not IgM 细菌上的抗体密度能调节单克隆 IgG 的 C1q 招募，但不能调节 IgM 的招募。

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-09-04 DOI: 10.1002/eji.202451228

Nathan Aymerich, Luca J. Schlotheuber, Olivia T. M. Bucheli, Kevin Portmann, Jean Baudry, Klaus Eyer

{"title":"Antibody density on bacteria regulates C1q recruitment by monoclonal IgG but not IgM","authors":"Nathan Aymerich, Luca J. Schlotheuber, Olivia T. M. Bucheli, Kevin Portmann, Jean Baudry, Klaus Eyer","doi":"10.1002/eji.202451228","DOIUrl":"10.1002/eji.202451228","url":null,"abstract":"Antibodies that trigger the complement system play a pivotal role in the immune defense against pathogenic bacteria and offer potential therapeutic avenues for combating antibiotic-resistant bacterial infections, a rising global concern. To gain a deeper understanding of the key parameters regulating complement activation by monoclonal antibodies, we developed a novel bioassay for quantifying classical complement activation at the monoclonal antibody level, and employed this assay to characterize rare complement-activating antibacterial antibodies on the single-antibody level in postimmunization murine antibody repertoires. We characterized monoclonal antibodies from various antibody isotypes against specific pathogenic bacteria (Bordetella pertussis and Neisseria meningitidis) to broaden the scope of our findings. We demonstrated activation of the classical pathway by individual IgM- and IgG-secreting cells, that is, monoclonal IgM and IgG2a/2b/3 subclasses. Additionally, we could observe different epitope density requirements for efficient C1q binding depending on antibody isotype, which is in agreement with previously proposed molecular mechanisms. In short, we found that antibody density most crucially regulated C1q recruitment by monoclonal IgG isotypes, but not IgM isotypes. This study provides additional insights into important parameters for classical complement initiation by monoclonal antibodies, a knowledge that might inform antibody screening and vaccination efforts.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"54 11","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202451228","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Colony stimulating factor 1 receptor (Csf1r) expressing cell ablation in mafia (macrophage-specific Fas-induced apoptosis) mice alters monocyte landscape and atherosclerotic lesion characteristics mafia（巨噬细胞特异性 Fas 诱导凋亡）小鼠中表达集落刺激因子 1 受体（Csf1r）的细胞消融会改变单核细胞分布和动脉粥样硬化病变特征。

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-09-04 DOI: 10.1002/eji.202350943

Indira Medina, Elias B Wieland, Lieve Temmerman, Jeroen J.T. Otten, Beatriz Bermudez, Ilze Bot, Timo Rademakers, Erwin Wijnands, Leon Schurgers, Barend Mees, Theo J.C. van Berkel, Pieter Goossens, Erik A.L. Biessen

{"title":"Colony stimulating factor 1 receptor (Csf1r) expressing cell ablation in mafia (macrophage-specific Fas-induced apoptosis) mice alters monocyte landscape and atherosclerotic lesion characteristics","authors":"Indira Medina, Elias B Wieland, Lieve Temmerman, Jeroen J.T. Otten, Beatriz Bermudez, Ilze Bot, Timo Rademakers, Erwin Wijnands, Leon Schurgers, Barend Mees, Theo J.C. van Berkel, Pieter Goossens, Erik A.L. Biessen","doi":"10.1002/eji.202350943","DOIUrl":"10.1002/eji.202350943","url":null,"abstract":"Macrophage infiltration and accumulation in the atherosclerotic lesion are associated with plaque progression and instability. Depletion of macrophages from the lesion might provide valuable insights into plaque stabilization processes. Therefore, we assessed the effects of systemic and local macrophage depletion on atherogenesis. To deplete monocytes/macrophages we used atherosclerosis-susceptible Apoe−/− mice, bearing a MaFIA (macrophage-Fas-induced-apoptosis) suicide construct under control of the Csf1r (CD115) promotor, where selective apoptosis of Csf1r-expressing cells was induced in a controlled manner, by administration of a drug, AP20187. Systemic induction of apoptosis resulted in a decrease in lesion macrophages and smooth-muscle cells. Plaque size and necrotic core size remained unaffected. Two weeks after the systemic depletion of macrophages, we observed a replenishment of the myeloid compartment. Myelopoiesis was modulated resulting in an expansion of CSF1Rlo myeloid cells in the circulation and a shift from Ly6chi monocytes toward Ly6cint and Ly6clo populations in the spleen. Local apoptosis induction led to a decrease in plaque burden and macrophage content with marginal effects on the circulating myeloid cells. Local, but not systemic depletion of Csf1r+ myeloid cells resulted in decreased plaque burden. Systemic depletion led to CSF1Rlo-monocyte expansion in blood, possibly explaining the lack of effects on plaque development.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"54 11","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202350943","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cover Story: Eur. J. Immunol. 9'24 封面故事Eur.J. Immunol.9'24

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-09-04 DOI: 10.1002/eji.202470091

引用次数: 0