John D Rioux, Gabrielle Boucher, Anik Forest, Bertrand Bouchard, Lise Coderre, Caroline Daneault, Isabelle Robillard Frayne, Julie Thompson Legault, Alain Bitton, Ashwin Ananthakrishnan, Sylvie Lesage, Ramnik J Xavier, Christine Des Rosiers
{"title":"Serum proteomic and metabolomic analyses from patients with IBD identify biological pathways associated with treatment success with anti-integrin therapy.","authors":"John D Rioux, Gabrielle Boucher, Anik Forest, Bertrand Bouchard, Lise Coderre, Caroline Daneault, Isabelle Robillard Frayne, Julie Thompson Legault, Alain Bitton, Ashwin Ananthakrishnan, Sylvie Lesage, Ramnik J Xavier, Christine Des Rosiers","doi":"10.1111/imcb.70039","DOIUrl":"https://doi.org/10.1111/imcb.70039","url":null,"abstract":"<p><p>Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases of the gastrointestinal tract believed to arise from an imbalance between its epithelial, immune and microbial components. It has been shown that biological differences (e.g. genetic, epigenetic, microbial, environmental) exist between patients with IBD. It is also known that there is important heterogeneity in the response to therapies that target very specific biological pathways (e.g. TNF-alpha signaling, IL-23R signaling, immune cell trafficking). The aim of this study was to identify potential biological differences associated with differential treatment response to the anti α4β7 integrin therapy known as vedolizumab. We performed targeted analyses of > 150 proteins and metabolites, and nontargeted analyses of > 1100 lipid entities in serum samples from 92 IBD patients (42 CD, 50 UC) immediately prior to initiation of therapy with vedolizumab (baseline samples) and at their first clinical assessment (week 14 samples). We detected that the baseline levels of multiple serum cytokines, amino acids, acylcarnitines and triglycerides were different between responders and nonresponders to treatment with vedolizumab. We also noted changes in serum analytes between baseline and week 14 samples that were different between these two groups of patients. Many of these serum analytes are markers of biological pathways that are involved in the activation, proliferation and metabolism of pro-inflammatory cells. This study provides support for the hypothesis that biological differences between individuals not only impact the risk to develop IBD and IBD-related clinical phenotypes but also an IBD patient's likelihood of responding to a biological therapy.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144281823","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}
Greta R Webb, Kerry L Hilligan, Sam I Old, Shiau-Choot Tang, Olivier Lamiable, Franca Ronchese
{"title":"Interferon signaling in type-2 dendritic cells supports T<sub>H</sub>2 and T follicular helper fates in response to allergens.","authors":"Greta R Webb, Kerry L Hilligan, Sam I Old, Shiau-Choot Tang, Olivier Lamiable, Franca Ronchese","doi":"10.1111/imcb.70035","DOIUrl":"https://doi.org/10.1111/imcb.70035","url":null,"abstract":"<p><p>Type-2 dendritic cells (DC2s) are essential for the initiation of type-2 immune responses, but the signaling pathways involved in allergen sensing, DC activation and instruction of CD4<sup>+</sup> T cell differentiation into T<sub>H</sub>2 cells remain unclear. Previous studies demonstrated a type-I interferon (IFN-I) signature in skin DC2s following immunization with non-viable larvae of the helminth Nippostrongylus brasiliensis (Nb), house dust mite (HDM) or Schistosoma egg antigen (SEA). Here we show that conditional loss of IFNAR1 signaling in CD11c<sup>+</sup> DCs significantly impaired T<sub>H</sub>2 effector and T follicular helper (TFH) CD4<sup>+</sup> T cell responses to Nb. In vivo proliferation experiments demonstrated reduced numbers of highly divided CD4<sup>+</sup> T cells in IFNAR1<sup>∆CD11c</sup> mice compared to IFNAR1<sup>WT</sup>, with similar proportions of GATA3<sup>hi</sup> T<sub>H</sub>2 cells within the divided populations indicating that IFNAR1 signaling in DCs was supporting T cell priming and expansion rather than GATA3<sup>hi</sup> differentiation. By contrast, TFHs were present in lower frequencies in IFNAR1<sup>∆CD11c</sup> mice compared to IFNAR1<sup>WT</sup>, suggesting that IFN-I signaling in DCs is necessary for allergen-specific TFH differentiation. Characterization of the DC2 compartment by flow cytometry and bulk RNAseq demonstrated lower numbers of Nb<sup>+</sup> DC2s in draining lymph nodes (dLN) and reduced expression of genes involved in DC2 motility, focal adhesion, and antigen processing, while expression of costimulatory molecules and cell survival and apoptosis pathway scores were similar. Therefore, IFN-I conditioning of skin DC2s is necessary for their effective priming of CD4<sup>+</sup> T<sub>H</sub>2 responses to allergens and likely acts through the additive effects of multiple IFN-I-regulated pathways in DC2s.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214494","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}
Capucine Bourel, Fernando Souza-Fonseca-Guimaraes, Sylvie Lesage
{"title":"Highlights of 2024: unleashing the power of NK cells-cancer's worst nightmare.","authors":"Capucine Bourel, Fernando Souza-Fonseca-Guimaraes, Sylvie Lesage","doi":"10.1111/imcb.70037","DOIUrl":"https://doi.org/10.1111/imcb.70037","url":null,"abstract":"<p><p>In this article for the Highlights of 2024 Series, we discuss strategies to enhance NK cell-based cancer therapies. These include (1) cytokine expression on bacterial membranes to boost NK cell activation in tumors, (2) optimizing CAR-NK cell manufacturing for improved efficacy, (3) using CRISPR-Cas9 to identify and target inhibitory genes, and (4) using tetraspecific engagers to enhance cytotoxicity and cytokine memory-like NK cells strengthening anti-tumor responses. This year's progress holds much promise for cancer treatments exploiting NK cells.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207280","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":"Platforms for studying cell-cell recognition by immune cells.","authors":"Jordan Kramer, P Anton van der Merwe, Omer Dushek","doi":"10.1111/imcb.70036","DOIUrl":"https://doi.org/10.1111/imcb.70036","url":null,"abstract":"<p><p>Immune cells interact directly with other cells and make decisions by integrating information from many different receptor-ligand interactions at these cell-cell interfaces. Since they encounter a huge variety of normal and abnormal cells, they experience many different combinations and concentrations of ligands. Understanding immune responses therefore requires platforms that enable ligands to be easily manipulated. We review and compare the available platforms, focusing on T-cell recognition. Although genetically modified antigen-presenting cells (APCs) offer the most physiological system, manipulating their ligands is difficult and slow. In contrast, solid surfaces or supported lipid bilayers allow easy manipulation of ligands but lack the biophysical properties of cells, such as softness, a glycocalyx, and/or ligand mobility. A recently developed CombiCell system enables easy manipulation of ligands while conserving key biophysical properties. By comparing the advantages and limitations of each platform, we provide a framework to choose the most suitable system to study signal integration in both basic and translational contexts.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172333","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":"Highlights of 2024: Advances in Germinal Centers.","authors":"Theresa E Pankhurst, Michelle A Linterman","doi":"10.1111/imcb.70032","DOIUrl":"https://doi.org/10.1111/imcb.70032","url":null,"abstract":"<p><p>In this article for the Highlights of 2024 series, we review the latest advances in the biology of the germinal center response. These discoveries provide key insights into germinal center function and dysregulation, uncovering new opportunities for the development of more effective vaccines.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092407","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}
Maria Miguel Cavaco, Pedro Gaspar, Rui do Amaral Vieira, Filipa Ribeiro, Luis Graca
{"title":"Heterogeneity of T follicular regulatory cells: exploring their expanding ontogeny and differentiation pathways.","authors":"Maria Miguel Cavaco, Pedro Gaspar, Rui do Amaral Vieira, Filipa Ribeiro, Luis Graca","doi":"10.1111/imcb.70026","DOIUrl":"https://doi.org/10.1111/imcb.70026","url":null,"abstract":"<p><p>T follicular regulatory (Tfr) cells have emerged as key mediators in controlling germinal center (GC) responses, preventing excessive immune activation and preserving self-tolerance. Initially thought to originate solely from thymic T regulatory cells (tTregs), recent findings reveal a more complex picture involving multiple differentiation pathways contributing to their heterogeneity. The natural route of differentiation comprises the most abundant subset, which originates from tTregs and retains the expression of CD25 (CD25<sup>+</sup> nTfr), before transitioning into a more mature CD25-negative state within the GC (CD25<sup>-</sup> nTfr). Conversely, the induced route (iTfr) includes Tfr cells that arise alongside nTfr cells but originate from peripheral Tregs or CD25-expressing Tfh cells, in addition to a late-GC subset (late Tfr) that emerges through the expression of FoxP3 by Tfh cells. The identification of circulating Tfr cells (cTfr) in peripheral blood, especially useful for studying immune dysregulation in humans, provides insights into their systemic roles and potential as biomarkers for immune dysfunction in different clinical scenarios. While it becomes evident that Tfr cells exhibit a heterogeneous nature, a deeper understanding of their distinct subsets could pave the way for targeted immunomodulatory strategies in the development of novel vaccines and therapeutics. This review provides a comprehensive overview of Tfr cell diversity, exploring their ontogeny, functional roles, and impact on immune homeostasis and disease.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092405","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}
Alex Johnston, Arti Medhavy, Suzanne Elliott, Danielle I Stanisic
{"title":"A trial-blazer in clinical research.","authors":"Alex Johnston, Arti Medhavy, Suzanne Elliott, Danielle I Stanisic","doi":"10.1111/imcb.70034","DOIUrl":"https://doi.org/10.1111/imcb.70034","url":null,"abstract":"<p><p>Founded in 2005, Gallipoli Medical Research (GMR) is a leading independent medical research institute located in Greenslopes, Brisbane, Queensland. GMR strives to enrich and restore lives through pioneering medical research that transcends the laboratory to deliver meaningful and tangible real-world solutions. In 2006, GMR launched its clinical trials program at one of Australia's largest private hospitals, with the focus on advancing healthcare through innovative treatments and emerging therapies, with a particular focus on oncology, liver, and respiratory diseases. Dr Suzanne Elliott is the Associate Director of Clinical Trials at GMR. Here, Dr Elliott discusses her transition from laboratory-based research into the clinical trial industry and shares her insight, advice, and pioneering contributions to industry, government, and the clinical trial research landscape across her diverse 30-year career.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101278","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}
Phillip J Whiley, Ojas VA Dixit, Mukta Das Gupta, Hardip Patel, Guoyan Zhao, Susan J Connor, Kim M Summers, David A Hume, Paul Pavli, Claire L O'Brien
{"title":"Transcriptomic signatures of host immune responses in aphthous ulcers, the earliest lesions of Crohn's disease, suggest that bacterial uptake, rather than global dysbiosis, is the initiating factor","authors":"Phillip J Whiley, Ojas VA Dixit, Mukta Das Gupta, Hardip Patel, Guoyan Zhao, Susan J Connor, Kim M Summers, David A Hume, Paul Pavli, Claire L O'Brien","doi":"10.1111/imcb.70031","DOIUrl":"10.1111/imcb.70031","url":null,"abstract":"<p>Crohn's disease is a chronic, transmural inflammatory disease of the human gut. Changes in the fecal microbial composition and dysbiosis are consistent features in studies of Crohn's disease patients, but whether dysbiosis is a cause or consequence of inflammation remains unresolved. Genetic susceptibility plays a role in the development of Crohn's disease and has been linked to genes involved in recognition of intestinal bacteria by the mononuclear phagocyte system. The earliest visible lesions in Crohn's disease are aphthous ulcers, overlying Peyer's patches and lymphoid follicles. To identify mechanisms underlying the earliest stages of disease we compared gene expression in aphthous ulcers, Peyer's patches, inflamed and endoscopically normal mucosa from patients and controls using total RNA-seq. The resulting data were subjected to network analysis to identify coregulated gene expression signatures of cell types and processes. These results were compared to single-cell RNA-seq analysis of intestinal macrophages in normal and diseased mucosa. The analysis of aphthous ulcers revealed signatures of epithelial stress and antimicrobial defense, plasma cell activation and immunoglobulin production, monocyte recruitment, inflammatory gene expression and induction of interferon-γ. These signatures were not present in the normal appearing mucosa adjacent to aphthous ulcers, which were similar to healthy control mucosa. Given the role of Peyer's patches and lymphoid follicles in sampling the luminal contents, these findings suggest the initial lesion in Crohn's disease arises from the uptake of bacteria and the activation of multiple host defense pathways rather than the breakdown of epithelial barrier integrity and widespread bacterial translocation.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":"103 5","pages":"473-484"},"PeriodicalIF":3.2,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imcb.70031","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092409","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}
Cassandra J McGill, Olivia S White, Ryan J Lu, Nirmal K Sampathkumar, Bérénice A Benayoun
{"title":"Sex-dimorphic gene regulation in murine macrophages across niches.","authors":"Cassandra J McGill, Olivia S White, Ryan J Lu, Nirmal K Sampathkumar, Bérénice A Benayoun","doi":"10.1111/imcb.70030","DOIUrl":"https://doi.org/10.1111/imcb.70030","url":null,"abstract":"<p><p>Macrophages are a key cell type of the innate immune system and are involved at all steps of inflammation: (i) they present antigens to initiate inflammation, (ii) they clear up foreign bodies through phagocytosis and (iii) they resolve inflammation by removing or deactivating mediator cells. Many subtypes of macrophages have been identified, classified by their niche and/or embryonic origin. In order to better develop therapies for conditions with macrophage dysfunction, it is crucial to decipher potential sex differences in key physiological mediators of inflammation so that treatment efficacy can be ensured regardless of biological sex. Here, we conduct a meta-analysis approach of transcriptomics data sets for male vs. female mouse macrophages across 8 niches to characterize conserved sex-dimorphic pathways in macrophages across origins and niches. For this purpose, we leveraged new and publicly available RNA-sequencing data sets from murine macrophages, preprocessed these datasets and filtered them based on objective QC criteria, and performed differential gene expression analysis using sex as the covariate of interest. Differentially expressed (DE) genes were compared across data sets and macrophage subsets, and functional enrichment analysis was performed to identify sex-specific functional differences. Consistent with their presence on the sex chromosomes, three genes were found differentially expressed across datasets (i.e. Xist, Eif2s3y and Ddx3y). More broadly, we found that female-biased pathways across niches are more consistent than male-biased pathways, specifically relating to the extracellular matrix. Our findings increase our understanding of transcriptional similarities across macrophage niches and underscore the importance of including sex as a biological variable in immune-related studies.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101279","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":"Building a thriving immunology community in Chile.","authors":"Maria Rosa Bono, Fabiola Osorio","doi":"10.1111/imcb.70033","DOIUrl":"https://doi.org/10.1111/imcb.70033","url":null,"abstract":"<p><p>The field of immunology in Chile has evolved remarkably over the past few decades, from a nascent discipline to a dynamic and rapidly developing community with significant international visibility. In this commentary, we, Fabiola Osorio and María Rosa Bono, offer personal reflections on the challenges and opportunities facing Chile's immunology community. As researchers who both returned to Chile after extensive training abroad, we have seen the dynamic nature of the Immunology field within our country. Our opinions also arise from our experiences as past presidents of the Chilean Association of Immunology (ASOCHIN; 2016-2019 MRB; 2019-2021 FO), the main scientific society congregating immunology researchers in Chile, where we have witnessed firsthand the growth of the local immunological community. Our testimonies and those of our colleagues highlight the resilience, creativity and collaborative spirit that have allowed Chile to carve out its place in global immunology.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075010","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}