Immunology & Cell Biology最新文献

{"title":"Glycolysis-Dependent Fatty Acid Metabolism Supports Human Tfh Cell Function.","authors":"Someshwar Nath Jha, Bhushan Nikam, Vivekananda Barik, Anuska Khatua, Deepak Jena, Shilpa Sachan, Mamuni Swain, Poonam Coshic, Sunil K Raghav, Nimesh Gupta","doi":"10.1111/imcb.70166","DOIUrl":"https://doi.org/10.1111/imcb.70166","url":null,"abstract":"<p><p>Follicular helper T (Tfh) cells orchestrate germinal center (GC) derived humoral immunity by providing essential help to B cells. Despite their key role in humoral immunity, the metabolic cues that shape Tfh cell differentiation and functions in humans remain poorly understood. Here, using a human ex vivo Tfh cell differentiation model, we investigated the metabolic requirements of Tfh cell development and function through targeted metabolic perturbation of glycolysis and fatty acid metabolism, transcriptomic analyses, and metabolic rescue experiments. Unexpectedly, early glycolytic inhibition enhanced Tfh cell differentiation but markedly impaired function, including reduced IL-21 production and diminished B-cell help. Transcriptomic and metabolic analyses revealed that glycolytic inhibition was accompanied by suppression of fatty acid metabolism. Consistently, independent inhibition of fatty acid synthesis or oxidation suppressed Tfh cell help functions, including IL-21 and IFN-γ production, as well as B-cell help potential. Interestingly, acetate supplementation partially restored IFN-γ secretion in glycolysis-inhibited conditions, but not IL-21, indicating limited metabolic compensation. Together, these findings reveal distinct metabolic requirements for Tfh cell differentiation and function and identify glycolysis-dependent fatty acid metabolism as an important determinant of human Tfh cell functional competence. This metabolic crosstalk provides new insight into the regulation of Tfh cells and Tfh-driven humoral immunity in vaccination and autoimmunity.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149190409","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":"Dual Host-Pathogen Screening of the Lung During Severe Influenza Using Spatial Transcriptomics.","authors":"Marcus Z W Tong, Oliver P Skinner, Chen Zhu, Brooke J Wanrooy, Ashlyn S Kerr, Zheng Ruan, Cameron G Williams, Heran Zhang, Linda M Wakim, Ashraful Haque","doi":"10.1111/imcb.70170","DOIUrl":"https://doi.org/10.1111/imcb.70170","url":null,"abstract":"<p><p>Here, we assessed whether spatially resolved capture of polyadenylated mRNA permitted simultaneous screening of host and viral responses in situ. Fresh-frozen lung samples from mice infected with H1N1 influenza A strain, PR8, were processed via genome-wide, spatial transcriptomics (ST) at 10-μm resolution. To determine if specific cell-types were detectable within the ST data, we first performed cellular deconvolution using publicly available, single-cell RNA-seq data of immune and non-immune cells from PR8-infected lungs. This revealed expected structures such as rings of epithelial cells lining airways, and at Day 10 post-infection (p.i.) unexpected structures dominated by B cells. We next screened ST data alone for groups of genes displaying similar spatial expression patterns. This again identified at Day 10 p.i. cellular aggregates enriched for genes associated with B cell biology. Mapping these gene signatures to a B cell transcriptomic atlas suggested plasmablasts had emerged early in the lung, which was confirmed by flow cytometry. Finally, by mapping ST data to the influenza A genome, we observed widespread expression of all 10 viral transcripts across samples at Day 4 but not Day 10 p.i., consistent with viral clearance. Cellular deconvolution analysis at Day 4 p.i. revealed proportions of every detected cell-type harbored viral transcripts, suggesting indiscriminate infection across the specific area of tissue examined. Subsequent whole-section immunohistochemical assessment further supported the phenomenon of localized indiscriminate infection, with these areas found adjacent to minimally infected zones. Thus, spatial screening of mRNA in tissues can simultaneously inform upon viral pathogenesis and host responses to infection.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163296","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":"The Leukocyte Landscape Across Mouse Strains and Tissues.","authors":"Ella Trolio, Sarah Dart, Liu Liu, Michaela Lucas, Amy Prosser","doi":"10.1111/imcb.70168","DOIUrl":"10.1111/imcb.70168","url":null,"abstract":"<p><p>With widespread use of mice (Mus musculus) in immunological research, understanding baseline immune variation between mouse models is critical. While peripheral blood immune profiles have been well-defined, strain- and sex-specific differences in leukocyte composition across other tissues remain poorly characterized. Here, we performed flow cytometric immunophenotyping of 19 leukocyte subsets and 3 T cell memory phenotypes in the blood, bone marrow, liver, spleen, and lymph nodes of seven strains of naïve adult male mice: Balb.b, BALB/c, BALB/c Ly5.1, C57BL/6J, C57BL/6J Ly5.1, BALB/c:B6J (F1), and DBA/2 J. Parallel analyses were conducted in female BALB/c and C57BL/6J mice. Each tissue contained a unique immunobiome, with conventional T and B cells enriched in the lymph nodes and spleen, unconventional T cells and innate lymphoid cells (ILCs) in the liver, and myeloid cells in the bone marrow. Generally, BALB-derived strains displayed a helper T cell- and innate-skewed profile, enriched for CD4 and regulatory T cells, neutrophils, and natural killer cells. C57BL/6J-derived strains were typically enriched for CD8 T cells, ILC1s, and conventional dendritic cells, consistent with a cytotoxic immune bias. Small differences were detected between congenic and parental strains. F1's exhibited a mix of C57BL/6J-biased and intermediate parental phenotypes. DBA/2 J mice were immunologically distinct, notably enriched for γδ T cells. Sex-associated differences were minor compared to strain effects. These findings provide tissue-specific benchmarks for leukocyte composition across commonly used mouse strains. They also highlight the importance of strain and sex selection and baseline immunophenotyping to support accurate interpretation of observed immune phenotypes in experimental contexts.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149134449","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":"Engineering Antibody Evolution: Germline-Targeting HIV Vaccines Reach a Turning Point.","authors":"Rowena A Bull, Deborah L Burnett","doi":"10.1111/imcb.70169","DOIUrl":"https://doi.org/10.1111/imcb.70169","url":null,"abstract":"<p><p>This commentary examines three recent Nature studies demonstrating a conceptual shift in HIV vaccine design, demonstrating how germline-targeting HIV vaccines can progress beyond expanding rare broad neutralizing antibody (bnAb) precursors to deliberately guiding their affinity maturation into bnAbs in non-human primates.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101514","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":"Ovarian Cancer-Associated Ascites Accumulates NK Lymphocytes Displaying a Transcriptomic Profile Consistent With the Immature/Secretory CD56bright Subtype","authors":"Caroline Natânia de Souza-Araújo,&nbsp;Glenerson Baptista,&nbsp;Gabriela Rapozo Guimarães,&nbsp;Raissa Carolina Alves da Silva,&nbsp;Adriana Yoshida,&nbsp;Cláudia Rodrigues Tonetti,&nbsp;José Andrés Yunes,&nbsp;Daniela Maira Cardoso,&nbsp;Sophie Derchain,&nbsp;Mariana Boroni,&nbsp;Fernando Guimarães","doi":"10.1111/imcb.70159","DOIUrl":"10.1111/imcb.70159","url":null,"abstract":"<p>Natural killer (NK) cells are important lymphocytes of the innate immune response against cancer. Based on their molecular and functional phenotypes, NK cells are categorized into two main subtypes known as CD56^dim and CD56^bright, which display distinct transcriptional profiles. Additionally, transcriptomic alterations may arise in response to different stimuli or microenvironmental conditions, ultimately affecting NK-cell functions. Here, RNA sequencing (RNAseq) was performed to characterize the transcriptomic profile of NK cells from epithelial ovarian cancer (EOC)-associated ascites. Two bulk RNAseq datasets were analyzed: one generated from samples collected from patients assisted at the Women's Hospital of the University of Campinas (CAISM-Unicamp, Brazil) and a second publicly available dataset obtained from the Gene Expression Omnibus database (GSE153713). Our transcriptomic analysis identified 5427 differentially expressed genes (DEGs; adjusted <i>p</i> &lt; 0.05), revealing extensive differences between ascites and blood NK cells. Furthermore, these findings indicated a possible shift in the biological program of ascites NK cells, from the conventional cytotoxic CD16⁺CD56^dim subtype to an immature/secretory CD56^bright profile. Comparison of ascites and blood NK RNAseq based on a previously defined transcriptional framework showed reduced NK1 and increased NK2 subtype scores in ascites, confirming association with distinct biological programs. In conclusion, ascites NK cells retain elements of the conventional NK-cell program while displaying a transcriptional profile distinct from peripheral blood NK cells, consistent with transcriptional remodeling to biological programs usually associated with the CD56^bright NK subtype.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":"104 9","pages":"896-905"},"PeriodicalIF":3.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imcb.70159","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148786280","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":"Mast Cells in Host Defense Against Cutaneous Staphylococcus aureus Infection","authors":"Hannah Dychtenberg,&nbsp;Carly Kadonoff,&nbsp;Bailey Lehnert,&nbsp;Priyanka Pundir","doi":"10.1111/imcb.70155","DOIUrl":"10.1111/imcb.70155","url":null,"abstract":"<p><i>Staphylococcus aureus</i> is an opportunistic pathogen implicated in skin and soft-tissue infections and chronic inflammatory skin diseases, such as atopic dermatitis. These infections can range from mild to potentially life-threatening systemic illnesses progressing to bacteremia, endocarditis, and sepsis. Mast cells, traditionally recognized for their role in allergies, are highly abundant within the skin and are gaining recognition for their contribution to bacterial defense. Here, we discuss the role of mast cells in three models of <i>S. aureus</i> skin infection according to skin depth: epicutaneous sensitization, intradermal injections, and subcutaneous injections. During <i>S. aureus</i> skin infection, mast cells become activated and accumulate in infected skin, recognize bacterial toxins, and modulate the activity of other immune cells, including neutrophils and dendritic cells. We discuss areas of research that should be the target of future studies, such as neuroimmunology, infected excisional wounds, and risk of systemic illness. Our review aims to bring attention to the host–pathogen interaction between mast cells and <i>S. aureus</i> in the skin, both to encourage deeper investigation and inform the development of immunomodulatory-based therapeutics.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":"104 9","pages":"867-880"},"PeriodicalIF":3.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imcb.70155","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148757178","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":"Genetic Risk Meets the Intestinal Barrier","authors":"J. L. E. Tearle,&nbsp;K. R. James","doi":"10.1111/imcb.70158","DOIUrl":"10.1111/imcb.70158","url":null,"abstract":"<p>Top: At increasing cellular resolution, the Alegbe et al. report that expression quantitative trait loci (eQTLs) are enriched in enhancer regions rather than promoters. They speculate that enhancer eQTLs only come into effect during certain cellular contexts, making them more tolerable. Bottom: Alegbe et al. identify an enrichment of eQTLs affecting Wnt pathway regulators in inflammatory bowel disease (IBD) epithelium, suggesting a reduced capacity for regeneration. Additionally, the authors show an enrichment of interaction eQTLs (ieQTLs) in IBD epithelium that become active only during inflammation.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":"104 9","pages":"864-866"},"PeriodicalIF":3.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imcb.70158","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148758576","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":"Lysosomal Rewiring Perpetuates Tumor Immune Evasion in Cancer","authors":"Nawal Al-Hoshani,&nbsp;Asad Ullah,&nbsp;Muhammad Muddassir Ali,&nbsp;Rania Ali El Hadi Mohamed","doi":"10.1111/imcb.70157","DOIUrl":"10.1111/imcb.70157","url":null,"abstract":"<p>Lysosomes are central regulators of cellular homeostasis, integrating catabolic and anabolic reactions to sustain metabolism. In cancer, however, lysosomal function is not merely upregulated but selectively rewired into distinct, context-dependent states that actively drive tumor immune evasion. This review proposes a conceptual framework linking metabolic, oxidative, oncogenic, and inflammatory pressures to six dominant lysosomal rewiring programs. Chronic nutrient deprivation and hypoxia activate AMPK-ULK1 and HIF signaling, promoting TFEB/TFE3-dependent lysosomal biogenesis, hyper-acidification, and autophagosome–lysosome fusion, collectively degrading immune effectors such as IL-1β and MHC complexes and impairing T-cell priming. Disseminated tumor cells exploit TPC2-mediated Ca²⁺ signaling and GLS1-dependent metabolism to buffer oxidative stress and support metastatic colonization, while dysregulated PI3K-AKT–mTOR and MYC signaling drive lysosomal peripheralization and lysosomal biogenesis through Arl8b-BORC-kinesin complexes, facilitating cathepsin-mediated exocytosis and MHC-I degradation. Chronic inflammation, sustained by tumor-associated macrophages, myeloid-derived suppressor cells, and IL-6/IL-10 gradients, further reinforce immune suppression. Beyond mechanisms, we also assess the translational readiness of the implicated molecular mediators, distinguishing those with established pharmacological outcomes, such as PI3K-AKT–mTOR inhibitors and repurposed chloroquine/hydroxychloroquine, from mediators that remain strictly preclinical, including TPC2, Arl8b-BORC, and CMTM6/DHHC3, or that are currently undruggable, such as TFEB/TFE3. By framing lysosomes as state-specific orchestrators of immune escape rather than uniform stress organelles, this review offers a mechanistic and translational roadmap for developing lysosome-directed strategies to restore anti-tumor immunity.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":"104 9","pages":"848-863"},"PeriodicalIF":3.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imcb.70157","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148756956","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":"The Imbalance Between Tumor Immunosurveillance and Tumor Immune Escape in Glioblastoma","authors":"Sarah J. MacDonald,&nbsp;Matthew Drill,&nbsp;Padmakrishnan C. Jayakrishnan,&nbsp;Richard P. Sequeira,&nbsp;Terence J. O'Brien,&nbsp;Rosalind L. Jeffree,&nbsp;Mastura Monif","doi":"10.1111/imcb.70153","DOIUrl":"10.1111/imcb.70153","url":null,"abstract":"<p>Cancer immunosurveillance is the immune-mediated identification and elimination of malignant cells and is an essential mechanism to inhibit cancer growth. However, during cancer progression, tumors evolve various strategies to evade effective immune-mediated eradication, a process termed tumor immune escape. Glioblastoma (GBM) is the most common form of primary brain cancer and illustrates the delicate balance between immune escape and effective immunosurveillance, and the subsequent consequences upon acquiring various strategies of evasion. GBM exhibits several strategies that drive tumor immune escape, including downregulating antigen presentation, inhibiting immune cell function, and fostering immunosuppression. This is further amplified by the tumor-promoting effects of other tumor microenvironment constituents, such as neurons and astrocytes, and the immune system's dual role in tumor suppression and tumor persistence. Collectively, this facilitates immunologically unchecked outgrowth, manifesting as a highly aggressive, treatment-resistant disease with a universally lethal outcome for patients with GBM.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":"104 9","pages":"881-895"},"PeriodicalIF":3.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imcb.70153","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148786198","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":"The Dysbiosis–Barrier–Immune Axis: Unraveling the Immune Consequences of Skin Microbial Imbalance","authors":"Ahmed Mahdy,&nbsp;Ismail Amin,&nbsp;Hend H. Mohamed,&nbsp;Mona Hamdy,&nbsp;Khaled Abuelhaded,&nbsp;Khaled M. Alam-ElDein,&nbsp;Omneya M. Elbakry,&nbsp;Adel Abdelkhalek,&nbsp;Mohamed Elkhawanky,&nbsp;Atef S. Elgebaly,&nbsp;Ahmed H. I. Faraag,&nbsp;Osama A. Mohammed,&nbsp;Ahmed S. Doghish","doi":"10.1111/imcb.70161","DOIUrl":"10.1111/imcb.70161","url":null,"abstract":"<p>The skin microbiota has been reframed as a dynamic and active regulator of cutaneous barrier integrity and immune programming, moving beyond its traditional view as a passive microbial community. Dysbiosis represents a complex functional and ecological imbalance that disrupts barrier integrity and may promote sustained inflammatory immune remodeling. This mechanistic axis, in which disruption of the microbiota contributes to barrier failure and immune dysregulation, underpins chronic inflammatory skin conditions. Conventional antibiotic-centered therapies often fail to restore microbial homeostasis or immune balance, highlighting their limitations. Emerging precision microbiome therapeutics focus on targeted modulation of microbial function, signaling pathways, and ecological restoration to repair barrier defects and recalibrate immune responses. This review synthesizes current evidence linking skin microbiota dysbiosis with barrier dysfunction, inflammatory immune remodeling, and emerging microbiome-directed therapeutic strategies. We propose an integrative framework linking ecological disruption, epithelial barrier injury, and immune dysregulation while highlighting unresolved mechanistic, translational, and knowledge gaps, such as detailed molecular mechanisms of host–microbiota interactions and challenges in translating findings into clinically effective personalized interventions. Future research should prioritize multi-omics integration and biomarker-driven stratification to advance precision dermatology therapeutics grounded in mechanistic insights of skin microbial ecology.</p>","PeriodicalId":179,"journal":{"name":"Immunology & Cell Biology","volume":"104 9","pages":"906-928"},"PeriodicalIF":3.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imcb.70161","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148862957","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}