Immunology & Cell Biology最新文献

{"title":"Transcriptional network analysis of peripheral blood leukocyte subsets in multiple sclerosis identifies a pathogenic role for a cytotoxicity-associated gene network in myeloid cells","authors":"Margaret A Jordan,&nbsp;Melissa M Gresle,&nbsp;Adrian T Gemiarto,&nbsp;Dragana Stanley,&nbsp;Letitia D Smith,&nbsp;Louise Laverick,&nbsp;Tim Spelman,&nbsp;Jim Stankovich,&nbsp;Annie ML Willson,&nbsp;Xuyen T Dinh,&nbsp;Laura Johnson,&nbsp;Kylie Robertson,&nbsp;Christopher AR Reid,&nbsp;Judith Field,&nbsp;Helmut Butzkueven,&nbsp;Alan G Baxter","doi":"10.1111/imcb.12793","DOIUrl":"10.1111/imcb.12793","url":null,"abstract":"<p>Multiple sclerosis (MS) is an autoimmune disease of the central nervous system affecting predominantly adults. It is a complex disease associated with both environmental and genetic risk factors. Although over 230 risk single-nucleotide polymorphisms have been associated with MS, all are common human variants. The mechanisms by which they increase the risk of MS, however, remain elusive. We hypothesized that a complex genetic phenotype such as MS could be driven by coordinated expression of genes controlled by transcriptional regulatory networks. We, therefore, constructed a gene coexpression network from microarray expression analyses of five purified peripheral blood leukocyte subsets of 76 patients with relapsing remitting MS and 104 healthy controls. These analyses identified a major network (or module) of expressed genes associated with MS that play key roles in cell-mediated cytotoxicity which was downregulated in monocytes of patients with MS. Manipulation of the module gene expression was achieved <i>in vitro</i> through small interfering RNA gene knockdown of identified drivers. In a mouse model, network gene knockdown modulated the autoimmune inflammatory MS model disease—experimental autoimmune encephalomyelitis. This research implicates a cytotoxicity-associated gene network in myeloid cells in the pathogenesis of MS.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":"102 8","pages":"702-720"},"PeriodicalIF":3.2,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imcb.12793","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141320107","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}

{"title":"Nurturing a positive research culture within your organization","authors":"Adrian Liston,&nbsp;Denise C Fitzgerald","doi":"10.1111/imcb.12795","DOIUrl":"10.1111/imcb.12795","url":null,"abstract":"<p>Positive research cultures provide the environment for scientists to explore ideas, grow as individuals, develop team science and create a positive impact on those around them. While positive research cultures need to grow from the kindness and integrity of team members, organization policy can either help or hinder this organic positive behavior. A focus on policies to enhance positive research culture can benefit even high-functioning organizations, by expanding and extending the benefits. Here we focus on key actionable areas to create and reinforce a positive research culture in your organization. We discuss the role of aligning staff recognition to the organization's missions, the influence of the organization unit and career structure on the research culture, the pyramid of building respectful interactions, the value of openness and transparency and the overarching goal of equality, diversity and inclusivity within the organization.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":"102 7","pages":"538-547"},"PeriodicalIF":3.2,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imcb.12795","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141316265","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}

{"title":"Impact of socioeconomic status on healthy immune responses in humans","authors":"Anthony Bertrand,&nbsp;Jamie Sugrue,&nbsp;Tianai Lou,&nbsp;Nollaig M Bourke,&nbsp;Lluis Quintana-Murci,&nbsp;Violaine Saint-André,&nbsp;Cliona O'Farrelly,&nbsp;Darragh Duffy,&nbsp;the Milieu Intérieur Consortium","doi":"10.1111/imcb.12789","DOIUrl":"10.1111/imcb.12789","url":null,"abstract":"<p>Individuals with low socioeconomic status (SES) are at greater risk of contracting and developing severe disease compared with people with higher SES. Age, sex, host genetics, smoking and cytomegalovirus (CMV) serostatus are known to have a major impact on human immune responses and thus susceptibility to infection. However, the impact of SES on immune variability is not well understood or explored. Here, we used data from the <i>Milieu Intérieur</i> project, a study of 1000 healthy volunteers with extensive demographic and biological data, to examine the effect of SES on immune variability. We developed an Elo-rating system using socioeconomic features such as education, income and home ownership status to objectively rank SES in the 1000 donors. We observed sex-specific SES associations, such as females with a low SES having a significantly higher frequency of CMV seropositivity compared with females with high SES, and males with a low SES having a significantly higher frequency of active smoking compared with males with a high SES. Using random forest models, we identified specific immune genes which were significantly associated with SES in both baseline and immune challenge conditions. Interestingly, many of the SES associations were sex stimuli specific, highlighting the complexity of these interactions. Our study provides a new way of computing SES in human populations that can help identify novel SES associations and reinforces biological evidence for SES-dependent susceptibility to infection. This should serve as a basis for further understanding the molecular mechanisms behind SES effects on immune responses and ultimately disease.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":"102 7","pages":"618-629"},"PeriodicalIF":3.2,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imcb.12789","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141305032","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}

{"title":"Decoding changes in tumor-infiltrating leukocytes through dynamic experimental models and single-cell technologies","authors":"Colin YC Lee,&nbsp;Menna R Clatworthy,&nbsp;David R Withers","doi":"10.1111/imcb.12787","DOIUrl":"10.1111/imcb.12787","url":null,"abstract":"<p>The ability to characterize immune cells and explore the molecular interactions that govern their functions has never been greater, fueled in recent years by the revolutionary advance of single-cell analysis platforms. However, precisely how immune cells respond to different stimuli and where differentiation processes and effector functions operate remain incompletely understood. Inferring cellular fate within single-cell transcriptomic analyses is now omnipresent, despite the assumptions typically required in such analyses. Recently developed experimental models support dynamic analyses of the immune response, providing insights into the temporal changes that occur within cells and the tissues in which such transitions occur. Here we will review these approaches and discuss how these can be combined with single-cell technologies to develop a deeper understanding of the immune responses that should support the development of better therapeutic options for patients.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":"102 8","pages":"665-679"},"PeriodicalIF":3.2,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imcb.12787","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141295217","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}

{"title":"Discovery of a monoclonal, high-affinity CD8+ T-cell clone following natural hepatitis C virus infection","authors":"Curtis Cai,&nbsp;Elizabeth Keoshkerian,&nbsp;Kristof Wing,&nbsp;Jerome Samir,&nbsp;Manuel Effenberger,&nbsp;Kilian Schober,&nbsp;Rowena A Bull,&nbsp;Andrew R Lloyd,&nbsp;Dirk H Busch,&nbsp;Fabio Luciani","doi":"10.1111/imcb.12791","DOIUrl":"10.1111/imcb.12791","url":null,"abstract":"<p>CD8⁺ T cells recognizing their cognate antigen are typically recruited as a polyclonal population consisting of multiple clonotypes with varying T-cell receptor (TCR) affinity to the target peptide–major histocompatibility complex (pMHC) complex. Advances in single-cell sequencing have increased accessibility toward identifying TCRs with matched antigens. Here we present the discovery of a monoclonal CD8⁺ T-cell population with specificity for a hepatitis C virus (HCV)–derived human leukocyte antigen (HLA) class I epitope (HLA-B*07:02 <i>GPRLGVRAT</i>) which was isolated directly <i>ex vivo</i> from an individual with an episode of acutely resolved HCV infection. This population was absent before infection and underwent expansion and stable maintenance for at least 2 years after infection as measured by HLA-multimer staining. Furthermore, the monoclonal clonotype was characterized by an unusually long dissociation time (half-life = 794 s and k_off = 5.73 × 10⁻⁴) for its target antigen when compared with previously published results. A comparison with related populations of HCV-specific populations derived from the same individual and a second individual suggested that high-affinity TCR–pMHC interactions may be inherent to epitope identity and shape the phenotype of responses which has implications for rational TCR selection and design in the age of personalized immunotherapies.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":"102 7","pages":"630-641"},"PeriodicalIF":3.2,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imcb.12791","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141295218","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}

{"title":"Highlight of 2023: Advances in pediatric immunology","authors":"Erika Van Nieuwenhove","doi":"10.1111/imcb.12790","DOIUrl":"10.1111/imcb.12790","url":null,"abstract":"<p>In this article for the Highlights of 2023 Series, significant advancements in pediatric immunology are discussed, focusing on new diagnostic and therapeutic approaches. Key studies include the integration of genomic and proteomic profiling for better diagnosis of inborn errors of immunity, the impact of nongenetic factors such as autoantibodies on immune responses, the promising use of Janus kinase inhibitors and chimeric antigen receptor-T cell therapy for treating immune deficiencies and autoimmune diseases and the potential for a curative approach using prime editing. These developments mark a shift toward personalized and precision medicine in pediatric immunology.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":"102 6","pages":"460-462"},"PeriodicalIF":3.2,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imcb.12790","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141282437","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}

{"title":"A Recipe for Success","authors":"Maike de la Roche","doi":"10.1111/imcb.12786","DOIUrl":"10.1111/imcb.12786","url":null,"abstract":"<p>In this article, I aim to give some pieces of career advise for young immunologists based on my own experiences.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":"102 7","pages":"554-556"},"PeriodicalIF":3.2,"publicationDate":"2024-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imcb.12786","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141198835","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}

{"title":"Designing interview questions to find the right candidate","authors":"Adrian Liston","doi":"10.1111/imcb.12788","DOIUrl":"10.1111/imcb.12788","url":null,"abstract":"<p>Asking the right questions during a job interview helps you find the best person for your team. A well-crafted question will allow the applicants to shed light on their skills and their passion for science. Just as importantly, good interview questions can let you know about the applicants’ support expectations and needs, and their approach to lab citizenship and research culture. Here we crowd-sourced the #ImmunologyFutures community for their go-to job interview questions, to help you find the right candidate for your position.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":"102 8","pages":"655-657"},"PeriodicalIF":3.2,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imcb.12788","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141178270","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}

{"title":"Loss of Bcl-3 regulates macrophage polarization by promoting macrophage glycolysis","authors":"Shengnan Liu,&nbsp;Hao Wang,&nbsp;Jiaoyang Li,&nbsp;Jingtao Gao,&nbsp;Li Yu,&nbsp;Xiaofei Wei,&nbsp;Mengchao Cui,&nbsp;Yuxin Zhao,&nbsp;Yinming Liang,&nbsp;Hui Wang","doi":"10.1111/imcb.12785","DOIUrl":"10.1111/imcb.12785","url":null,"abstract":"<p>M1/M2 macrophage polarization plays an important role in regulating the balance of the microenvironment within tissues. Moreover, macrophage polarization involves the reprogramming of metabolism, such as glucose and lipid metabolism. Transcriptional coactivator B-cell lymphoma-3 (Bcl-3) is an atypical member of the IκB family that controls inflammatory factor levels in macrophages by regulating nuclear factor kappa B pathway activation. However, the relationship between Bcl-3 and macrophage polarization and metabolism remains unclear. In this study, we show that the knockdown of Bcl-3 in macrophages can regulate glycolysis-related gene expression by promoting the activation of the nuclear factor kappa B pathway. Furthermore, the loss of Bcl-3 was able to promote the interferon gamma/lipopolysaccharide-induced M1 macrophage polarization by accelerating glycolysis. Taken together, these results suggest that Bcl-3 may be a candidate gene for regulating M1 polarization in macrophages.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":"102 7","pages":"605-617"},"PeriodicalIF":3.2,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141156960","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}

{"title":"Improving the Quality of Adolescent and Youth-Friendly Health Services Through Integrated Supportive Supervision in Four Nigerian States.","authors":"Dorcas Akila, Akinola Oluwasegun, Krishna Bose, Olukunle Omotoso, Adewale Adefila, Lisa Mwaikambo","doi":"10.9745/GHSP-D-22-00169","DOIUrl":"10.9745/GHSP-D-22-00169","url":null,"abstract":"<p><strong>Background: </strong>Although the unique sexual and reproductive health needs of adolescents and youth (AY) are widely recognized, the challenge remains how to integrate adolescent- and youth-friendly health services (AYFHS) effectively within a systems-based approach that is both feasible and scalable. This article provides preliminary evidence from 4 Nigerian states that sought to overcome this challenge by implementing capacity-strengthening approaches centered around a shortened quality assurance (QA) tool that has become part of the state health system's routine supportive supervision process and follow-up quality improvement (QI) activities.</p><p><strong>Methods: </strong>A shortened QA tool was administered to assess and track the performance of 130 high-volume health facilities across 5 domains to serve its AY population with quality contraceptive services. Facility-based providers (N=198) received training on adolescent and youth sexual and reproductive health, AYFHS, and long-acting reversible contraceptive methods. To corroborate checklist findings, we conducted exit interviews with 754 clients (aged 15-24 years) who accessed contraceptive services from the facilities that met the World Health Organization's minimum standards for quality AYFHS.</p><p><strong>Results: </strong>In the 4 states, the QA tool was applied at baseline and 2 rounds, accompanied by QI capacity strengthening after each round. At baseline, only 12% of the 130 facilities in the 4 states scored met the minimum quality standards for AYFHS. After 2 rounds, 88% of the facilities met the minimum standards. AY client volume increased over this same period. All 4 states showed great improvements; however, the achievements varied by state. The exit interview feedback supported client satisfaction with the services provided to AY.</p><p><strong>Conclusion: </strong>Integrating QA followed by QI within Nigeria's family planning supportive supervision system is not only feasible but also impacts the quality of AYFHS and contraceptive uptake by clients aged 15-24 years.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":"72 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11111107/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72403340","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}