In this Research Highlight, we discuss recent research which shows that TCR-mediated activation and NF-κB signalling play an indispensable role in localising Xist RNA and its interactors to the inactive X chromosome (Xi) in T cells (left and middle). Inhibition of NF-κB disrupts this process, impairing the recruitment of silencing factors and jeopardizing the maintenance of X chromosome inactivation (right).
{"title":"An X-tra role for NFκB in gene regulation?","authors":"Sara Berent, Rhys S Allan","doi":"10.1111/imcb.12850","DOIUrl":"https://doi.org/10.1111/imcb.12850","url":null,"abstract":"<p><p>In this Research Highlight, we discuss recent research which shows that TCR-mediated activation and NF-κB signalling play an indispensable role in localising Xist RNA and its interactors to the inactive X chromosome (Xi) in T cells (left and middle). Inhibition of NF-κB disrupts this process, impairing the recruitment of silencing factors and jeopardizing the maintenance of X chromosome inactivation (right).</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142963473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Penny Hawkins, James Dooley, Jessica Rodda, Colin Gilbert
This report presents findings from a group of UK-based researchers with expertise in the use of animal models for bone marrow ablation and reconstitution. The primary aim is to facilitate the implementation of the Three Rs (Replacement, Reduction and Refinement), with an emphasis on refinement. Bone marrow ablation and reconstitution procedures are performed for a number of different purposes and conducted predominantly in mice. These procedures can induce significant suffering, classified as "severe", Category E or Category D/E under European, US and Canadian legislation, respectively. Although severity categorization is not mandated in countries such as Australia and New Zealand, legislation still requires that the level of animal suffering must be minimized to the greatest extent possible. This report identifies specific animal welfare issues and proposes practical measures aimed at reducing both animal use and suffering.
{"title":"Refining bone marrow ablation and reconstitution in mice.","authors":"Penny Hawkins, James Dooley, Jessica Rodda, Colin Gilbert","doi":"10.1111/imcb.12847","DOIUrl":"https://doi.org/10.1111/imcb.12847","url":null,"abstract":"<p><p>This report presents findings from a group of UK-based researchers with expertise in the use of animal models for bone marrow ablation and reconstitution. The primary aim is to facilitate the implementation of the Three Rs (Replacement, Reduction and Refinement), with an emphasis on refinement. Bone marrow ablation and reconstitution procedures are performed for a number of different purposes and conducted predominantly in mice. These procedures can induce significant suffering, classified as \"severe\", Category E or Category D/E under European, US and Canadian legislation, respectively. Although severity categorization is not mandated in countries such as Australia and New Zealand, legislation still requires that the level of animal suffering must be minimized to the greatest extent possible. This report identifies specific animal welfare issues and proposes practical measures aimed at reducing both animal use and suffering.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pursuing an international scientific career is a fantastic opportunity for personal and professional growth, but it also poses unique challenges, which can be particularly daunting for researchers coming from resource-limited countries. Drawing from personal experience, this article provides insights into navigating the transition to working abroad in academia and developing a sustainable career while integrating into a new culture. From predeparture preparations to achieving career independence, I discuss practical aspects of crafting tailored applications to contact potential advisers, contemplating visa-related challenges, establishing collaborations and emphasizing the value of finding appropriate mentorship to help you adapt to new cultural and professional environments. The article also underscores the importance of resilience, adaptability and redefining career success as a dynamic, nonlinear process. I present an original perspective on career planning, inspired by maritime voyage planning, to address the complexities of balancing personal and professional life, particularly during transitional periods. This approach, which combines four key stages of planning, namely, appraisal, planning, execution and monitoring, serves as a model for early-career researchers to navigate the unpredictable tides of academic work and personal life abroad with the goal of sustaining progress and well-being. These reflections aim to empower scientists preparing for or adapting to international research environments, fostering resilience and adaptability for long-term success abroad.
{"title":"Learnings from ten years away from \"home\" as a South American immunologist in Ireland.","authors":"Natalia Muñoz-Wolf","doi":"10.1111/imcb.12849","DOIUrl":"https://doi.org/10.1111/imcb.12849","url":null,"abstract":"<p><p>Pursuing an international scientific career is a fantastic opportunity for personal and professional growth, but it also poses unique challenges, which can be particularly daunting for researchers coming from resource-limited countries. Drawing from personal experience, this article provides insights into navigating the transition to working abroad in academia and developing a sustainable career while integrating into a new culture. From predeparture preparations to achieving career independence, I discuss practical aspects of crafting tailored applications to contact potential advisers, contemplating visa-related challenges, establishing collaborations and emphasizing the value of finding appropriate mentorship to help you adapt to new cultural and professional environments. The article also underscores the importance of resilience, adaptability and redefining career success as a dynamic, nonlinear process. I present an original perspective on career planning, inspired by maritime voyage planning, to address the complexities of balancing personal and professional life, particularly during transitional periods. This approach, which combines four key stages of planning, namely, appraisal, planning, execution and monitoring, serves as a model for early-career researchers to navigate the unpredictable tides of academic work and personal life abroad with the goal of sustaining progress and well-being. These reflections aim to empower scientists preparing for or adapting to international research environments, fostering resilience and adaptability for long-term success abroad.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01Epub Date: 2024-06-27DOI: 10.1111/imcb.12797
Lidia Yshii
This Commentary recounts an academic journey from dentistry to neuroimmunology, highlighting pivotal moments such as a PhD fraught with challenges and an unexpected postdoctoral experience in France. My decision to settle in Belgium for a postdoc and subsequent transition to an assistant professorship at KU Leuven reflects resilience, adaptability and a commitment to both scientific exploration and family life. Balancing career uncertainties, motherhood and academic achievements, it encapsulates a trajectory shaped by a passion for neuroimmunology.
{"title":"From dentistry to immunology: navigating challenges and building a career in neuroimmunology.","authors":"Lidia Yshii","doi":"10.1111/imcb.12797","DOIUrl":"10.1111/imcb.12797","url":null,"abstract":"<p><p>This Commentary recounts an academic journey from dentistry to neuroimmunology, highlighting pivotal moments such as a PhD fraught with challenges and an unexpected postdoctoral experience in France. My decision to settle in Belgium for a postdoc and subsequent transition to an assistant professorship at KU Leuven reflects resilience, adaptability and a commitment to both scientific exploration and family life. Balancing career uncertainties, motherhood and academic achievements, it encapsulates a trajectory shaped by a passion for neuroimmunology.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":" ","pages":"12-14"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141454176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01Epub Date: 2024-11-17DOI: 10.1111/imcb.12837
Céline Pattaroni
In this article, we discuss a recently published study by Gopee et al., who have unveiled a surprising role for macrophages in human prenatal skin development, extending far beyond their traditional immune function. By constructing a comprehensive multi-omics single-cell atlas of human prenatal skin, they demonstrate that innate immune cells play a key role in hair follicle formation, scarless wound healing and neurovascular development.
{"title":"Prenatal Skin Cell Atlas reveals macrophages' role beyond immunity.","authors":"Céline Pattaroni","doi":"10.1111/imcb.12837","DOIUrl":"10.1111/imcb.12837","url":null,"abstract":"<p><p>In this article, we discuss a recently published study by Gopee et al., who have unveiled a surprising role for macrophages in human prenatal skin development, extending far beyond their traditional immune function. By constructing a comprehensive multi-omics single-cell atlas of human prenatal skin, they demonstrate that innate immune cells play a key role in hair follicle formation, scarless wound healing and neurovascular development.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":" ","pages":"6-8"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01Epub Date: 2024-12-06DOI: 10.1111/imcb.12842
Cyril Seillet, Le Xiong
A recent article has shown that blocking NKp46 signaling reduces injury, highlighting these cells as key drivers of organ damage and potential therapeutic targets in autoimmune diseases. In lupus nephritis, NKp46+ ILC1s orchestrate kidney inflammation by producing CSF2, driving the expansion of pro-inflammatory macrophages that infiltrate epithelial niches and exacerbate tissue damage.
{"title":"ILC1 as critical gatekeepers in autoimmune kidney damage.","authors":"Cyril Seillet, Le Xiong","doi":"10.1111/imcb.12842","DOIUrl":"10.1111/imcb.12842","url":null,"abstract":"<p><p>A recent article has shown that blocking NKp46 signaling reduces injury, highlighting these cells as key drivers of organ damage and potential therapeutic targets in autoimmune diseases. In lupus nephritis, NKp46<sup>+</sup> ILC1s orchestrate kidney inflammation by producing CSF2, driving the expansion of pro-inflammatory macrophages that infiltrate epithelial niches and exacerbate tissue damage.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":" ","pages":"9-11"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01Epub Date: 2024-11-28DOI: 10.1111/imcb.12838
Antje Haap-Hoff, Michael Freeley, Eugene Dempsey, Dara Dunican, Emily Bennett, Denise Triglia, Joanna Skubis-Zegadlo, Anthony Mitchell Davies, Dermot Kelleher, Aideen Long
The αLβ2 integrin LFA-1 plays a key role in T-cell adhesion to the endothelial vasculature and migration into both secondary lymphoid organs and peripheral tissues via interactions with its target protein ICAM-1, but the pathways that regulate LFA-1-mediated T-cell polarity and migration are not fully understood. In this study we screened two RNAi libraries targeting G protein-coupled receptors (GPCR)/GPCR-associated proteins and kinases in a HuT 78 T cell line model of LFA-1-stimulated T-cell migration. Based on staining of the actin cytoskeleton, multiple parameters to measure cell morphology were used to assess the contribution of 1109 genes to LFA-1-mediated T-cell polarity and migration. These RNAi screens identified a number of both novel and previously identified genes that either increased or decreased the polarity and migratory capacity of these cells. Following multiparametric analysis, hierarchical clustering and pathway analysis, three of these genes were characterized in further detail using primary human T cells, revealing novel roles for the heterotrimeric G protein subunit Gβ1 and Casein Kinase 2 in LFA-1-mediated T-cell polarity and migration in vitro. Our studies also highlighted a new role for ICAP-1, an adaptor protein previously described to be associated with β1 integrins, in β2 integrin LFA-1-directed migration in T cells. Knockdown of ICAP-1 expression in primary T cells revealed a role in cell polarity, cell velocity and transmigration towards SDF-1 for this adaptor protein. This study therefore uncovers new roles for GPCR/GPCR-associated proteins and kinases in T-cell migration and provides potential novel targets for modulation of the T-cell immune response.
αLβ2整合素LFA-1在T细胞粘附到内皮血管以及通过与其靶蛋白ICAM-1相互作用迁移到次级淋巴器官和外周组织的过程中起着关键作用,但调控LFA-1介导的T细胞极性和迁移的途径尚未完全清楚。在这项研究中,我们筛选了两个针对G蛋白偶联受体(GPCR)/GPCR相关蛋白和激酶的RNAi文库,在HuT 78 T细胞系模型中研究了LFA-1刺激的T细胞迁移。在肌动蛋白细胞骨架染色的基础上,使用多种参数测量细胞形态,以评估1109个基因对LFA-1介导的T细胞极性和迁移的贡献。这些 RNAi 筛选发现了一些新基因和以前发现的基因,它们增加或减少了这些细胞的极性和迁移能力。经过多参数分析、层次聚类和通路分析,我们利用原代人类 T 细胞对其中三个基因进行了进一步的详细鉴定,发现了异三聚 G 蛋白亚基 Gβ1 和酪蛋白激酶 2 在 LFA-1 介导的体外 T 细胞极性和迁移中的新作用。我们的研究还强调了ICAP-1在T细胞中β2整合素LFA-1定向迁移中的新作用,ICAP-1是一种适配蛋白,以前曾被描述为与β1整合素相关。通过敲除原代 T 细胞中 ICAP-1 的表达,发现了这种适配蛋白在细胞极性、细胞速度和向 SDF-1 迁移中的作用。因此,这项研究揭示了 GPCR/GPCR 相关蛋白和激酶在 T 细胞迁移中的新作用,并为调节 T 细胞免疫反应提供了潜在的新靶点。
{"title":"RNAi library screening reveals Gβ1, Casein Kinase 2 and ICAP-1 as novel regulators of LFA-1-mediated T cell polarity and migration.","authors":"Antje Haap-Hoff, Michael Freeley, Eugene Dempsey, Dara Dunican, Emily Bennett, Denise Triglia, Joanna Skubis-Zegadlo, Anthony Mitchell Davies, Dermot Kelleher, Aideen Long","doi":"10.1111/imcb.12838","DOIUrl":"10.1111/imcb.12838","url":null,"abstract":"<p><p>The α<sub>L</sub>β<sub>2</sub> integrin LFA-1 plays a key role in T-cell adhesion to the endothelial vasculature and migration into both secondary lymphoid organs and peripheral tissues via interactions with its target protein ICAM-1, but the pathways that regulate LFA-1-mediated T-cell polarity and migration are not fully understood. In this study we screened two RNAi libraries targeting G protein-coupled receptors (GPCR)/GPCR-associated proteins and kinases in a HuT 78 T cell line model of LFA-1-stimulated T-cell migration. Based on staining of the actin cytoskeleton, multiple parameters to measure cell morphology were used to assess the contribution of 1109 genes to LFA-1-mediated T-cell polarity and migration. These RNAi screens identified a number of both novel and previously identified genes that either increased or decreased the polarity and migratory capacity of these cells. Following multiparametric analysis, hierarchical clustering and pathway analysis, three of these genes were characterized in further detail using primary human T cells, revealing novel roles for the heterotrimeric G protein subunit Gβ1 and Casein Kinase 2 in LFA-1-mediated T-cell polarity and migration in vitro. Our studies also highlighted a new role for ICAP-1, an adaptor protein previously described to be associated with β1 integrins, in β2 integrin LFA-1-directed migration in T cells. Knockdown of ICAP-1 expression in primary T cells revealed a role in cell polarity, cell velocity and transmigration towards SDF-1 for this adaptor protein. This study therefore uncovers new roles for GPCR/GPCR-associated proteins and kinases in T-cell migration and provides potential novel targets for modulation of the T-cell immune response.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":" ","pages":"73-92"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11688611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142737913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01Epub Date: 2024-11-09DOI: 10.1111/imcb.12835
Fabiana Corsi-Zuelli
As a young scientist in Brazil, my journey began with a modest education in a public school system that often lacked the resources needed to provide students with comprehensive support. However, with persistence and determination, I successfully gained admission to the University of São Paulo, a prestigious institution and one of the top universities in Latin America. My research focuses on the relationship between the nervous and immune systems in psychosis, a topic I am deeply passionate about. In this piece, I will discuss the systemic issues within the Brazilian education and research systems and delve deeper into my own challenges and achievements as a young scientist in Brazil, sharing insights that can inspire others in similar situations.
{"title":"The journey of young scientists in Brazil: challenges and perspectives.","authors":"Fabiana Corsi-Zuelli","doi":"10.1111/imcb.12835","DOIUrl":"10.1111/imcb.12835","url":null,"abstract":"<p><p>As a young scientist in Brazil, my journey began with a modest education in a public school system that often lacked the resources needed to provide students with comprehensive support. However, with persistence and determination, I successfully gained admission to the University of São Paulo, a prestigious institution and one of the top universities in Latin America. My research focuses on the relationship between the nervous and immune systems in psychosis, a topic I am deeply passionate about. In this piece, I will discuss the systemic issues within the Brazilian education and research systems and delve deeper into my own challenges and achievements as a young scientist in Brazil, sharing insights that can inspire others in similar situations.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":" ","pages":"22-26"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01Epub Date: 2024-07-11DOI: 10.1111/imcb.12810
Johnathan Canton
My path to becoming a scientist has taken many twists and turns. This is perhaps not unusual to hear. Indeed, in discussions with my colleagues it seems that for many of us the path was never a straight one. Certainly, for me there have been moments when my whole world was encompassed by science and at other times, I have felt strongly that my time in science was up. I like to think that as scientists we ask a lot of questions and, for many of us, those questions extend to our very purpose as a scientist. My intention with this article is not to document my career path in detail or to provide very specific advice. Rather, I hope to describe how questions have defined my journey and to inspire others to occasionally pause and ask themselves what a career in science means to them. Today, I am an Assistant Professor at a major Canadian university, and here are the questions I asked along the way.
{"title":"From the bench to the farm and back again.","authors":"Johnathan Canton","doi":"10.1111/imcb.12810","DOIUrl":"10.1111/imcb.12810","url":null,"abstract":"<p><p>My path to becoming a scientist has taken many twists and turns. This is perhaps not unusual to hear. Indeed, in discussions with my colleagues it seems that for many of us the path was never a straight one. Certainly, for me there have been moments when my whole world was encompassed by science and at other times, I have felt strongly that my time in science was up. I like to think that as scientists we ask a lot of questions and, for many of us, those questions extend to our very purpose as a scientist. My intention with this article is not to document my career path in detail or to provide very specific advice. Rather, I hope to describe how questions have defined my journey and to inspire others to occasionally pause and ask themselves what a career in science means to them. Today, I am an Assistant Professor at a major Canadian university, and here are the questions I asked along the way.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":" ","pages":"15-18"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}