Journal of immunology最新文献

{"title":"Lipin-1 restrains macrophage lipid synthesis to promote inflammation resolution.","authors":"Temitayo T Bamgbose, Robert M Schilke, Oluwakemi O Igiehon, Ebubechukwu H Nkadi, Monika Binwal, David Custis, Sushma Bharrhan, Benjamin Schwarz, Eric Bohrnsen, Catharine M Bosio, Rona S Scott, Arif Yurdagul, Brian N Finck, Matthew D Woolard","doi":"10.1093/jimmun/vkae010","DOIUrl":"10.1093/jimmun/vkae010","url":null,"abstract":"<p><p>Macrophages are critical to maintaining and restoring tissue homeostasis during inflammation. The lipid metabolic state of macrophages influences their function and polarization, which is crucial to the resolution of inflammation. The contribution of lipid synthesis to proinflammatory macrophage responses is well understood. However, how lipid synthesis regulates proresolving macrophage responses needs to be better understood. Lipin-1 is a phosphatidic acid phosphatase with a transcriptional coregulatory activity that regulates lipid metabolism. We previously demonstrated that lipin-1 supports proresolving macrophage responses, and here, myeloid-associated lipin-1 is required for inflammation resolution, yet how lipin-1-regulated cellular mechanisms promote macrophage proresolution responses is unknown. We demonstrated that the loss of lipin-1 in macrophages led to increased free fatty acid, neutral lipid, and ceramide content and increased phosphorylation of acetyl-CoA carboxylase. The inhibition of the first step of lipid synthesis, the transport of citrate from the mitochondria, reduced lipid content and restored efferocytosis and inflammation resolution in lipin-1mKO mice and macrophages. Our findings suggest macrophage-associated lipin-1 restrains lipid synthesis, promoting proresolving macrophage function in response to proresolving stimuli.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"214 1","pages":"85-103"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844145/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615044","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}

{"title":"The neurorepellent SLIT2 inhibits LPS-induced proinflammatory signaling in macrophages.","authors":"Marko Skrtic, Bushra Yusuf, Sajedabanu Patel, Emily C Reddy, Kenneth K Y Ting, Myron I Cybulsky, Spencer A Freeman, Lisa A Robinson","doi":"10.1093/jimmun/vkae009","DOIUrl":"10.1093/jimmun/vkae009","url":null,"abstract":"<p><p>Macrophages are important mediators of immune responses with critical roles in the recognition and clearance of pathogens, as well as in the resolution of inflammation and wound healing. The neuronal guidance cue SLIT2 has been widely studied for its effects on immune cell functions, most notably directional cell migration. Recently, SLIT2 has been shown to directly enhance bacterial killing by macrophages, but the effects of SLIT2 on inflammatory activation of macrophages are less known. Using RNA sequencing analysis, quantitative polymerase chain reaction, and enzyme-linked immunosorbent assay, we determined that in murine bone marrow-derived macrophages challenged with the potent proinflammatory mediator lipopolysaccharide (LPS), exposure to the bioactive N-terminal fragment of SLIT2 (NSLIT2) suppressed production of proinflammatory cytokines interleukin (IL)-6 and IL-12 and concurrently increased the anti-inflammatory cytokine IL-10. We found that NSLIT2 inhibited LPS-induced MyD88- and TRIF-mediated signaling cascades and did not inhibit LPS-induced internalization of Toll-like receptor 4 (TLR4), but instead inhibited LPS-induced upregulation of macropinocytosis. Inhibition of macropinocytosis in macrophages attenuated LPS-induced production of proinflammatory IL-6 and IL-12 and concurrently enhanced anti-inflammatory IL-10. Taken together, our results indicate that SLIT2 can selectively modulate macrophage response to potent proinflammatory stimuli, such as LPS, by attenuating proinflammatory activation and simultaneously enhancing anti-inflammatory activity. Our results highlight the role of macropinocytosis in proinflammatory activation of macrophages exposed to LPS. Given that LPS-producing bacteria cause host illness through synergistic direct bacterial infection and excessive LPS-induced systemic inflammation, our work suggests a novel therapeutic role for SLIT2 in combatting the significant morbidity and mortality of patients with Gram-negative bacterial sepsis.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"214 1","pages":"141-152"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615412","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}

{"title":"Impact of obesity on the CCR6-CCL20 axis in epidermal γδ T cells and IL-17A production in murine wound healing and psoriasis.","authors":"William Lawler, Tanya Castellanos, Emma Engel, Cristian R Alvizo, Antolette Kasler, Savannah Bshara-Corson, Julie M Jameson","doi":"10.1093/jimmun/vkae011","DOIUrl":"10.1093/jimmun/vkae011","url":null,"abstract":"<p><p>Obesity is associated with comorbidities including type 2 diabetes, chronic nonhealing wounds, and psoriasis. Normally, skin homeostasis and repair is regulated through the production of cytokines and growth factors derived from skin-resident cells including epidermal γδ T cells. However, epidermal γδ T cells exhibit reduced proliferation and defective growth factor and cytokine production during obesity and type 2 diabetes. One of the genes modulated in epidermal γδ T cells during obesity and type 2 diabetes is CCR6, which is the receptor for CCL20. CCL20 is elevated in the skin during obesity and type 2 diabetes. Here, we identify a subset of murine epidermal γδ T cells that express CCR6 upon activation, both in vitro and in vivo. We show that CCL20 stimulates epidermal γδ T cells to produce interleukin (IL)-17, indicating that CCR6 regulates the IL-17 axis in epidermal γδ T cells. In murine models of wound repair and psoriasis, these epidermal γδ T cells upregulate CCR6 and produce IL-17, with obesity amplifying this response during wound repair but having less effect during psoriasis. These findings have novel implications for the regulation of a specific population of IL-17-producing epidermal γδ T cells during skin damage and inflammation.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"214 1","pages":"153-166"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615673","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}

{"title":"PVR exposure influences the activation, adhesion, and protein expression of human CD8+ T cells, including the CD96-mediated transfer of PVR.","authors":"Xueting Huang, Girija Pawge, Christina E Snicer, Chia-Hung Christine Hsiao, Andrew J Wiemer","doi":"10.1093/jimmun/vkae002","DOIUrl":"https://doi.org/10.1093/jimmun/vkae002","url":null,"abstract":"<p><p>Poliovirus receptor (PVR) ligands have gained attention as immunotherapy targets, yet their regulation remains unclear. Here, we examine the impact of PVR exposure on primary human CD8+ T cells. We used flow cytometry and Western blot analysis to quantify expression of PVR and its ligands in naïve and effector T cells and used adhesion assays and enzyme-linked immunosorbent assay (ELISA) to assess the impact of PVR on T cell adhesion and cytokine production. Stimulation with phytohemagglutinin P strongly increased DNAM-1 expression and caused a less robust and more variable increase in TIGIT expression. Exposure to PVR-Fc enhanced the CD8+ T cell adhesion to ICAM-1-coated plates in a dose-dependent manner, while exposure to PVR-expressing K32 cells mildly decreased CD8+ T cell interferon γ release. However, PVR exposure strongly decreased the expression of DNAM-1, TIGIT, and CD96. The reduction of DNAM-1, TIGIT, and CD96 induced by PVR was dominant to the increase caused by T cell receptor signaling. The impact of PVR on their expression was completely abolished by the Q63R and F128R point mutations of PVR, while DNAM-1 was partially rescued by inhibitors of Src and protein kinase C. Additionally, PVR exposure along with T cell receptor signaling promoted the transfer of surface proteins including PVR from K32 cells to CD8+ T cells. This PVR transfer was mediated by the IgV domain of PVR and CD96 on CD8+ T cells and required cellular contact. Our findings collectively demonstrate that PVR engagement has a mild antagonistic effect on interferon γ production but strongly impacts CD8+ T cell adhesion and protein expression.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"214 1","pages":"55-71"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615407","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":"Early expansion of TIGIT+PD1+ effector memory CD4 T cells via agonistic effect of alefacept in new-onset type 1 diabetes.","authors":"Lauren E Higdon, Laura A Cooney, Elisavet Serti, Duangchan Suwannasaen, Virginia S Muir, Alice E Wiedeman, Kristina M Harris, Jorge Pardo, Mark S Anderson, Cate Speake, Gerald T Nepom, Peter S Linsley, Srinath Sanda, S Alice Long","doi":"10.1093/jimmun/vkae014","DOIUrl":"10.1093/jimmun/vkae014","url":null,"abstract":"<p><p>The CD2-depleting drug alefacept (LFA3-Ig) preserved beta cell function in new-onset type 1 diabetes (T1D) patients. The most promising biomarkers of response were late expansion of exhausted CD8 T cells and rare baseline inflammatory islet-reactive CD4 T cells, neither of which can be used to measure responses to drug in the weeks after treatment. Thus, we investigated whether early changes in T cell immunophenotypes could serve as biomarkers of drug activity. We characterized T cell responses by flow cytometry and identified an exhausted-like population of CD2low CD4 effector memory T cells coexpressing TIGIT and PD1 that expanded by 11 wk after the start of treatment. This population was not entirely spared from alefacept-mediated depletion in vivo or in vitro but recovered through homeostatic proliferation of CD2low cells in vivo. Proliferation of TIGIT+PD1+ effector memory CD4 T cells increased with treatment, with a concomitant reduction of proinflammatory cytokine production. The persistent increase of TIGIT+PD1+ effector memory CD4 T cells was specific to alefacept treatment; 2 other T cell depleting therapies, teplizumab and anti-thymocyte globulin, induced only a transient increase in this CD4 population. Our data suggest that the expanding TIGIT+PD1+ effector memory CD4 T cell population represents a promising biomarker of early treatment effects of alefacept. The nondepleting effects on proliferation and cytokine production also suggest agonistic activity by this CD2 targeted therapy.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"214 1","pages":"12-22"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615641","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}

{"title":"Genetic evidence for the suppressive role of zebrafish vhl targeting mavs in antiviral innate immunity during RNA virus infection.","authors":"Xueyi Sun, Wen Liu, Chunchun Zhu, Zixuan Wang, Hongyan Deng, Qian Liao, Wuhan Xiao, Xing Liu","doi":"10.1093/jimmun/vkae017","DOIUrl":"https://doi.org/10.1093/jimmun/vkae017","url":null,"abstract":"<p><p>The von Hippel-Lindau (VHL) tumor suppressor gene VHL is a classic tumor suppressor that has been identified in family members with clear cell renal cell carcinomas, central nervous system and retinal hemangioblastomas, phaeochromocytomas, and pancreatic neuroendocrine tumors. The well-defined function of VHL is to mediate proteasomal degradation of hydroxylated hypoxia-inducible factor α proteins, resulting in the downregulation of hypoxia-responsive gene expression. Previously, we reported that VHL inhibits antiviral signaling by targeting mitochondrial antiviral signaling protein (MAVS) for proteasomal degradation. However, due to the lack of a viable animal model, the physiological role and underlying mechanism of VHL in antiviral immunity remains to be elucidated. In this study, we found that heterozygous vhl-deficient zebrafish have normal neutrophils and no gross phenotypic alterations. However, upon spring viremia of carp virus or grass carp reovirus infection, antiviral gene expression is induced in vhl+/- zebrafish compared with wild-type zebrafish. In addition, spring viremia of carp virus replication is suppressed in vhl+/- zebrafish, owing to the enhancement of antiviral ability. Furthermore, by crossing with mavs-/- zebrafish line, we observed that disruption of mavs in vhl+/- zebrafish abrogates the viral resistance exhibited in vhl+/- zebrafish. Thus, we reveal that heterozygous vhl deficiency enhances the antiviral ability of zebrafish against RNA virus infection, and we provide genetic evidence to support that zebrafish mavs serves as a mediator for the suppressive role of vhl in antiviral innate immunity.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"214 1","pages":"167-179"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615671","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":"Suppression of NF-κB and downstream XBP1 by DcR3 contributes to a decrease in antibody secretion.","authors":"Po-Chun Liu, Szu-Ying Huang, Kuo-I Lin, Shie-Liang Hsieh, Chuen-Miin Leu","doi":"10.1093/jimmun/vkae005","DOIUrl":"https://doi.org/10.1093/jimmun/vkae005","url":null,"abstract":"<p><p>Decoy receptor 3 (DcR3), a soluble receptor in the tumor necrosis factor receptor superfamily, regulates the functions of monocytes, macrophages, dendritic cells, and T cells. Previous studies have demonstrated that DcR3 suppresses B cell proliferation in vitro and ameliorates autoimmune diseases in animal models; however, whether and how DcR3 regulates antibody production is unclear. Using a DcR3 transgenic mouse model, we found that DcR3 impaired the T cell-dependent antigen-stimulated antibody response. The number of Ag-specific antibody-secreting cells was transiently reduced, but the concentration of specific antibodies continued to decrease in the DcR3 transgenic mice, implying a direct suppression of antibody production by DcR3. In vitro assays showed that the DcR3-Fc fusion protein attenuated T cell-dependent induced antibody production and reduced the expression of secretory Igh and Xbp1. We found that nuclear factor κB (NF-κB) activity was essential for the expression of Xbp1 in activated B cells. DcR3-Fc attenuated anti-CD40-induced NF-κB activity and Xbp1 promoter activity. Furthermore, DcR3-Fc decreased the expression of Xbp1 in Blimp1+ antibody-secreting cells. Restoration of spliced XBP1 (X-box binding protein 1) in DcR3-treated B cells increased the secretory Ighg1 transcript levels, suggesting that reducing XBP1 is one of the mechanisms by which DcR3 regulates antibody production both in vitro and in vivo. Collectively, these results indicate that in addition to blocking proliferation, DcR3 impairs NF-κB activation, subsequently decreasing the expression of Xbp1, eventually leading to a reduction in antibody secretion.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"214 1","pages":"72-84"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615408","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":"Influenza 5xM2e mRNA lipid nanoparticle vaccine confers broad immunity and significantly enhances the efficacy of inactivated split vaccination when coadministered.","authors":"Phillip Grovenstein, Noopur Bhatnagar, Ki-Hye Kim, Surya Sekhar Pal, Chau Thuy Tien Le, Jannatul Ruhan Raha, Rong Liu, Chong Hyun Shin, Bo Ryoung Park, Lanying Du, Jeeva Subbiah, Bao-Zhong Wang, Sang-Moo Kang","doi":"10.1093/jimmun/vkae013","DOIUrl":"10.1093/jimmun/vkae013","url":null,"abstract":"<p><p>Current influenza vaccines are not effective in conferring protection against antigenic variants and pandemics. To improve cross-protection of influenza vaccination, we developed a 5xM2e messenger RNA (mRNA) vaccine encoding the tandem repeat conserved ectodomain (M2e) of ion channel protein M2 derived from human, swine, and avian influenza A viruses. The lipid nanoparticle (LNP)-encapsulated 5xM2e mRNA vaccine was immunogenic, eliciting high levels of M2e-specific IgG antibodies, IFN-γ+ T cells, T follicular helper cells, germinal center phenotypic B cells, and plasma cells. The mice with 5xM2e mRNA vaccination were broadly protected against lethal infection regardless of hemagglutinin (H1, H3, H5) subtypes by preventing severe weight loss. Injection of 5xM2e mRNA LNP vaccine induced acute innate responses recruiting monocytes, macrophages, and diverse subsets of dendritic cells. A single dose of combined 5xM2e mRNA LNP and split vaccines resulted in significantly enhanced and sustainable IgG antibody responses to viral antigens and protection against homologous and heterologous viruses. This study provides a new strategy of combined mRNA and seasonal vaccination, significantly enhancing vaccine protective efficacy.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"214 1","pages":"104-114"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844137/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615674","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}

{"title":"ISG15 Drives Immune Pathology and Respiratory Failure during Systemic Lymphocytic Choriomeningitis Virus Infection.","authors":"Namir Shaabani, Jaroslav Zak, Jennifer L Johnson, Zhe Huang, Nhan Nguyen, Daniel C Lazar, Vincent F Vartabedian, Nadine Honke, Joseph G Jardine, Jordan Woehl, Marco Prinz, Klaus-Peter Knobeloch, Kei-Ichiro Arimoto, Dong-Er Zhang, Sergio D Catz, John R Teijaro","doi":"10.4049/jimmunol.2400042","DOIUrl":"10.4049/jimmunol.2400042","url":null,"abstract":"<p><p>ISG15, an IFN-stimulated gene, plays a crucial role in modulating immune responses during viral infections. Its upregulation is part of the host's defense mechanism against viruses, contributing to the antiviral state of cells. However, altered ISG15 expression can also lead to immune dysregulation and pathological outcomes, particularly during persistent viral infections. Understanding the balance of ISG15 in promoting antiviral immunity while avoiding immune-mediated pathology is essential for developing targeted therapeutic interventions against viral diseases. In this article, using Usp18-deficient, USP18 enzymatic-inactive and Isg15-deficient mouse models, we report that a lack of USP18 enzymatic function during persistent viral infection leads to severe immune pathology characterized by hematological disruptions described by reductions in platelets, total WBCs, and lymphocyte counts; pulmonary cytokine amplification; lung vascular leakage; and death. The lack of Usp18 in myeloid cells mimicked the pathological manifestations observed in Usp18-/- mice and required Isg15. Mechanistically, interrupting the enzymes that conjugate/deconjugate ISG15, using Uba7-/- or Usp18C61A mice, respectively, led to accumulation of ISG15 that was accompanied by inflammatory neutrophil accumulation, lung pathology, and death similar to that observed in Usp18-deficient mice. Moreover, myeloid cell depletion reversed pathological manifestations, morbidity, and mortality in Usp18C61A mice. Our results suggest that dysregulated ISG15 production and signaling during persistent lymphocytic choriomeningitis virus infection can produce lethal immune pathology and could serve as a therapeutic target during severe viral infections with pulmonary pathological manifestations.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":"1811-1824"},"PeriodicalIF":3.6,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11784630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568219","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}

{"title":"Identification of a Specific Granular Marker of Zebrafish Eosinophils Enables Development of New Tools for Their Study.","authors":"Miriam Herbert, Christian Goosmann, Volker Brinkmann, Christiane Dimmler, Mark R Cronan","doi":"10.4049/jimmunol.2400259","DOIUrl":"10.4049/jimmunol.2400259","url":null,"abstract":"<p><p>Eosinophils control many aspects of the vertebrate innate immune response. They contribute to homeostasis, inflammatory conditions and defense against pathogens. With the varied functions of eosinophils, they have been found to play both protective and pathogenic roles in many diseases. The zebrafish (Danio rerio) has emerged as a useful model organism for human diseases but tools to study eosinophils in this model are severely limited. Here, we characterize a new and highly specific marker gene, embp, for eosinophils in zebrafish and report a new transgenic reporter line using this gene to visualize eosinophils in vivo. In addition, we created an Embp-specific polyclonal Ab that allows the identification of eosinophils ex vivo. These new tools expand the approaches for studying eosinophils in the zebrafish model. Using these reagents, we have been able to identify Embp as a constituent of eosinophil granules in zebrafish. These advances will allow for the investigation of eosinophil biology in the zebrafish model organism, allowing researchers to identify the contribution of eosinophils to the many diseases that are modeled within zebrafish and also shed light on the evolution of eosinophils within vertebrates.</p>","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":"1893-1901"},"PeriodicalIF":3.6,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11605671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502049","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}