European Journal of Immunology最新文献_第7页

Langerhans cells orchestrate apoptosis of DNA-damaged keratinocytes upon high-dose UVB skin exposure 朗格汉斯细胞在高剂量紫外线照射皮肤时协调 DNA 损坏的角质细胞凋亡

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-09-17 DOI: 10.1002/eji.202451020

Daniela Ortner, Helen Strandt, Christoph H. Tripp, Sarah Spoeck, Athanasios Seretis, Florian Hornsteiner, Sophie Dieckmann, Matthias Schmuth, Patrizia Stoitzner

{"title":"Langerhans cells orchestrate apoptosis of DNA-damaged keratinocytes upon high-dose UVB skin exposure","authors":"Daniela Ortner, Helen Strandt, Christoph H. Tripp, Sarah Spoeck, Athanasios Seretis, Florian Hornsteiner, Sophie Dieckmann, Matthias Schmuth, Patrizia Stoitzner","doi":"10.1002/eji.202451020","DOIUrl":"10.1002/eji.202451020","url":null,"abstract":"Ultraviolet (UV) irradiation of the skin causes mutations that can promote the development of melanoma and nonmelanoma skin cancer. High-dose UVB exposure triggers a vigorous skin reaction characterized by inflammation resulting in acute sunburn. This response includes the formation of sunburn cells and keratinocytes (KC) undergoing programmed cell death (apoptosis) when repair mechanisms of DNA damage are inadequate. The primary objective of this research was to clarify the involvement of Langerhans cells (LC) in the development of acute sunburn following intense UVB skin irradiation. To address this, we subjected the dorsal skin of mice to a single high-dose UVB exposure and analyzed the immediate immune response occurring within the skin tissue. Acute sunburn triggered an activation of LC, coinciding with a rapid influx of neutrophils that produced TNF-α. Furthermore, our investigation unveiled a marked increase in DNA-damaged KC and the subsequent induction of apoptosis in these cells. Importantly, we demonstrate a crucial link between the inflammatory cascade, the initiation of apoptosis in DNA-damaged KC, and the presence of LC in the skin. LC were observed to modulate the chemokine response in the skin following exposure to UVB, thereby affecting the trafficking of neutrophils. Skin lacking LC revealed diminished inflammation, contained fewer TNF-α-producing neutrophils, and due to the prevention of apoptosis induction, a lingering population of DNA-damaged KC, presumably carrying the risk of enduring genomic alterations. In summary, our results underscore the pivotal role of LC in preserving the homeostasis of UVB-irradiated skin. These findings contribute to a deeper understanding of the intricate mechanisms underlying acute sunburn responses and their implications for UV-induced skin cancer.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"54 12","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202451020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142247799","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

In vitro modulation of T cells in myasthenia gravis by low-dose IL-2 小剂量 IL-2 对肌无力 T 细胞的体外调节作用

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-09-17 DOI: 10.1002/eji.202451268

Merve Çebi, Arman Çakar, Hacer Durmuş, Onur Akan, Fikret Aysal, Yeşim Parman, Güher Saruhan-Direskeneli

{"title":"In vitro modulation of T cells in myasthenia gravis by low-dose IL-2","authors":"Merve Çebi, Arman Çakar, Hacer Durmuş, Onur Akan, Fikret Aysal, Yeşim Parman, Güher Saruhan-Direskeneli","doi":"10.1002/eji.202451268","DOIUrl":"10.1002/eji.202451268","url":null,"abstract":"Follicular helper (Tfh), peripheral helper (Tph), and regulatory (Treg) T cells are involved in myasthenia gravis (MG) pathogenesis, an autoimmune disorder arising from autoantibodies targeting neuromuscular junction proteins. This study explores the impact of low-dose IL-2 on Tfh, Tph, and Treg cells in vitro in MG. Acetylcholine-receptor antibody-positive MG (AChR-MG), muscle-specific kinase antibody-positive MG (MuSK-MG) patients, and healthy controls (HC) were studied. Blood cells were cultured with/without IL-2 and compared by the ratios of IL-2 stimulated/unstimulated cultures. In both AChR-MG and MuSK-MG patients, CD25+FoxP3+Tregs were lower, while CXCR5+PD-1+ or ICOS+Tfh and CXCR5−PD-1+ or ICOS+Tph cells were higher compared with HC. Among the MG group, the FoxP3+ Treg cells in AChR-MG patients were even lower compared with MuSK-MG patients. In vitro IL-2 stimulation increased Tregs in all groups while decreasing PD-1+/ICOS+Tfh and PD-1+/ICOS+Tph populations. The fold-increase ratio of Tregs and the fold-decrease ratio of PD-1+ or ICOS+Tfh and ICOS+Tph cells in AChR-MG and MuSK-MG patients were greater than in HCs. Low-dose IL-2 treatment may balance Tfh, Tph, and Treg cells in MG patients, offering a potential opportunity for disease modulation.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"54 11","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202451268","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142268289","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

γδ T cells in immune-mediated kidney disease 免疫性肾病中的γδ T 细胞

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-09-17 DOI: 10.1002/eji.202451069

Alex Waterhölter, Christian F. Krebs, Ulf Panzer

{"title":"γδ T cells in immune-mediated kidney disease","authors":"Alex Waterhölter, Christian F. Krebs, Ulf Panzer","doi":"10.1002/eji.202451069","DOIUrl":"10.1002/eji.202451069","url":null,"abstract":"Immune-mediated kidney diseases, including glomerulonephritis (GN), represent a diverse spectrum of disorders characterized by inflammation within the glomerulus and other renal compartments. Despite recent advances, the immunopathogenesis of these diseases remains incompletely understood. Current therapeutic approaches based on nonspecific immunosuppression often result in suboptimal outcomes and significant side effects, highlighting the need for tailored interventions. The complexity of the immune system extends beyond classical T-cell immunity, with the emergence of unconventional T cells — γδ T cells, NKT cells, and MAIT cells — that exhibit a semi-invariant nature and unique functions that bridge innate and adaptive immunity. γδ T cells exhibit unique homing and activation mechanisms and respond to different ligands, implying a multifaceted role in immune regulation. The understanding of γδ T-cell involvement in kidney disease lags behind conventional T-cell research. However, advances in immune cell analysis technologies offer promising avenues for elucidating their precise functions. This review synthesizes the current knowledge on γδ T cells in renal diseases, explores potential therapeutic strategies, and presents a roadmap for future research directions.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"54 12","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202451069","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142247798","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

Lipid nanoparticle-mediated RNA delivery for immune cell modulation 脂质纳米粒子介导的 RNA 递送用于免疫细胞调节。

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-09-16 DOI: 10.1002/eji.202451008

Emily H. Kim, Sridatta V. Teerdhala, Marshall S. Padilla, Ryann A. Joseph, Jacqueline J. Li, Rebecca M. Haley, Michael J. Mitchell

引用次数: 0

The power of many: Multilevel targeting of representative chemokine and metabolite GPCRs in personalized cancer therapy 众人拾柴火焰高：多层次靶向具有代表性的趋化因子和代谢物 GPCRs，实现个性化癌症治疗

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-09-12 DOI: 10.1002/eji.202350870

Donato Inverso, Carlotta Tacconi, Serena Ranucci, Marco De Giovanni

引用次数: 0

Complement-targeted therapeutics: Are we there yet, or just getting started? 补体靶向疗法：我们是成功了，还是刚刚起步？

IF 4.5 3区医学

European Journal of Immunology Pub Date : 2024-09-12 DOI: 10.1002/eji.202350816

Daniel Ricklin

{"title":"Complement-targeted therapeutics: Are we there yet, or just getting started?","authors":"Daniel Ricklin","doi":"10.1002/eji.202350816","DOIUrl":"10.1002/eji.202350816","url":null,"abstract":"Therapeutic interventions in the complement system, a key immune-inflammatory mediator and contributor to a broad range of clinical conditions, have long been considered important yet challenging or even unfeasible to achieve. Almost 20 years ago, a spark was lit demonstrating the clinical and commercial viability of complement-targeted therapies. Since then, the field has experienced an impressive expansion of targeted indications and available treatment modalities. Currently, a dozen distinct complement-specific therapeutics covering several intervention points are available in the clinic, benefiting patients suffering from eight disorders, not counting numerous clinical trials and off-label uses. Observing this rapid rise of complement-targeted therapy from obscurity to mainstream with amazement, one might ask whether the peak of this development has now been reached or whether the field will continue marching on to new heights. This review looks at the milestones of complement drug discovery and development achieved so far, surveys the currently approved drug entities and indications, and ventures a glimpse into the future advancements yet to come.","PeriodicalId":165,"journal":{"name":"European Journal of Immunology","volume":"54 12","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/eji.202350816","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142175813","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

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":"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":"54 12","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628899/pdf/","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":"OA","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":"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":"54 12","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628907/pdf/","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":"OA","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":"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":"54 12","pages":""},"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":"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":"54 12","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628923/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0