Nature Immunology最新文献

{"title":"The diverse roles of neutrophils from protection to pathogenesis","authors":"Rana Herro, H. Leighton Grimes","doi":"10.1038/s41590-024-02006-5","DOIUrl":"10.1038/s41590-024-02006-5","url":null,"abstract":"Neutrophil granulocytes are the most abundant leukocytes in the blood and constitute a critical arm of innate immunity. They are generated in the bone marrow, and under homeostatic conditions enter the bloodstream to patrol tissues and scout for potential pathogens that they quickly destroy through phagocytosis, intracellular degradation, release of granules and formation of extracellular traps. Thus, neutrophils are important effector cells involved in antibacterial defense. However, neutrophils can also be pathogenic. Emerging data suggest they have critical functions related to tissue repair and fibrosis. Moreover, similarly to other innate immune cells, neutrophil cell states are affected by their microenvironment. Notably, this includes tumors that co-opt neutrophils. Neutrophils can undergo transcriptional and epigenetic reprogramming, thus causing or modulating inflammation and injury. It is also possible that distinct neutrophil subsets are generated with designated functions in the bone marrow. Understanding neutrophil plasticity and alternative cell states will help resolve their contradictive roles. This Review summarizes the most recent key findings surrounding protective versus pathogenic functions of neutrophils; elaborating on phenotype-specific subsets of neutrophils and their involvement in homeostasis and disease. In this Review, Herro and Grimes summarize the most recent key findings surrounding protective versus pathogenic functions of neutrophils, elaborating on phenotype-specific subsets of neutrophils and their involvement in homeostasis and disease.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"25 12","pages":"2209-2219"},"PeriodicalIF":27.7,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142673215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Remodeling of Il4-Il13-Il5 locus underlies selective gene expression","authors":"Hiroyuki Nagashima, Justin Shayne, Kan Jiang, Franziska Petermann, Aleksandra Pękowska, Yuka Kanno, John J. O’Shea","doi":"10.1038/s41590-024-02007-4","DOIUrl":"10.1038/s41590-024-02007-4","url":null,"abstract":"The type 2 cytokines, interleukin (IL)-4, IL-13 and IL-5 reside within a multigene cluster. Both innate (ILC2) and adaptive T helper 2 (TH2) lymphocytes secrete type 2 cytokines with diverse production spectra. Using transcription factor footprint and chromatin accessibility, we systemically cataloged regulatory elements (REs) denoted as SHS-I/II, KHS-I/II, +6.5kbIl13, 5HS-I(a, b, c, d, e), 5HS-II and 5HS-III(a, b, c) across the extended Il4-Il13-Il5 locus in mice. Physical proximities among REs were coordinately remodeled in three-dimensional space after cell activation, leading to divergent compartmentalization of Il4, Il13 and Il5 with varied combinations of REs. Deletions of REs revealed no single RE solely accounted for selective regulation of a given cytokine in vivo. Instead, individual RE differentially contribute to proper genomic positioning of REs and target genes. RE deletions resulted in context-dependent dysregulation of cytokine expression and immune response in tissue. Thus, signal-dependent remodeling of three-dimensional configuration underlies divergent cytokine outputs from the type 2 loci. O’Shea and colleagues examine the three-dimensional chromatin architecture of the type 2 cytokine locus and how it differs between innate ILC2 cells and adaptive TH2 lymphocytes.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"25 12","pages":"2220-2233"},"PeriodicalIF":27.7,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142673220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Author Correction: NK cell receptor NKG2D sets activation threshold for the NCR1 receptor early in NK cell development","authors":"Vedrana Jelenčić, Marko Šestan, Inga Kavazović, Maja Lenartić, Sonja Marinović, Tim D. Holmes, Michaela Prchal-Murphy, Berislav Lisnić, Veronika Sexl, Yenan T. Bryceson, Felix M. Wensveen, Bojan Polić","doi":"10.1038/s41590-024-02038-x","DOIUrl":"10.1038/s41590-024-02038-x","url":null,"abstract":"","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 1","pages":"146-146"},"PeriodicalIF":27.7,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41590-024-02038-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142670684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"B cells infiltrate cutaneous T cell lymphomas","authors":"","doi":"10.1038/s41590-024-02022-5","DOIUrl":"10.1038/s41590-024-02022-5","url":null,"abstract":"Cutaneous T cell lymphoma is a rare, difficult to diagnose malignancy of T cells. Malignant T cells, together with populations of stromal cells and B cells, shape their own tumor niche for improved cancer cell survival in the skin.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"25 12","pages":"2180-2181"},"PeriodicalIF":27.7,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142670685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cutaneous T cell lymphoma atlas reveals malignant TH2 cells supported by a B cell-rich tumor microenvironment","authors":"Ruoyan Li, Johanna Strobl, Elizabeth F. M. Poyner, Aya Balbaa, Fereshteh Torabi, Pavel V. Mazin, Nana-Jane Chipampe, Emily Stephenson, Ciro Ramírez-Suástegi, Vijaya Baskar Mahalingam Shanmugiah, Louis Gardner, Bayanne Olabi, Rowen Coulthard, Rachel A. Botting, Nina Zila, Elena Prigmore, Nusayhah H. Gopee, Marta A. Chroscik, Efpraxia Kritikaki, Justin Engelbert, Issac Goh, Hon Man Chan, Harriet F. Johnson, Jasmine Ellis, Victoria Rowe, Win Tun, Gary Reynolds, Dexin Yang, April Rose Foster, Laure Gambardella, Elena Winheim, Chloe Admane, Benjamin Rumney, Lloyd Steele, Laura Jardine, Julia Nenonen, Keir Pickard, Jennifer Lumley, Philip Hampton, Simeng Hu, Fengjie Liu, Xiangjun Liu, David Horsfall, Daniela Basurto-Lozada, Louise Grimble, Chris M. Bacon, Sophie C. Weatherhead, Hanna Brauner, Yang Wang, Fan Bai, Nick J. Reynolds, Judith E. Allen, Constanze Jonak, Patrick M. Brunner, Sarah A. Teichmann, Muzlifah Haniffa","doi":"10.1038/s41590-024-02018-1","DOIUrl":"10.1038/s41590-024-02018-1","url":null,"abstract":"Cutaneous T cell lymphoma (CTCL) is a potentially fatal clonal malignancy of T cells primarily affecting the skin. The most common form of CTCL, mycosis fungoides, can be difficult to diagnose, resulting in treatment delay. We performed single-cell and spatial transcriptomics analysis of skin from patients with mycosis fungoides-type CTCL and an integrated comparative analysis with human skin cell atlas datasets from healthy and inflamed skin. We revealed the co-optation of T helper 2 (TH2) cell-immune gene programs by malignant CTCL cells and modeling of the tumor microenvironment to support their survival. We identified MHC-II+ fibroblasts and dendritic cells that can maintain TH2 cell-like tumor cells. CTCL tumor cells are spatially associated with B cells, forming tertiary lymphoid structure-like aggregates. Finally, we validated the enrichment of B cells in CTCL and its association with disease progression across three independent patient cohorts. Our findings provide diagnostic aids, potential biomarkers for disease staging and therapeutic strategies for CTCL. Haniffa and colleagues provide diagnostic aids, potential biomarkers for disease staging and therapeutic strategies for cutaneous T cell lymphoma.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"25 12","pages":"2320-2330"},"PeriodicalIF":27.7,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41590-024-02018-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142665528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disease-associated B cells and immune endotypes shape adaptive immune responses to SARS-CoV-2 mRNA vaccination in human SLE","authors":"Caterina E. Faliti, Trinh T. P. Van, Fabliha A. Anam, Narayanaiah Cheedarla, M. Elliott Williams, Ashish Kumar Mishra, Sabeena Y. Usman, Matthew C. Woodruff, Geoff Kraker, Martin C. Runnstrom, Shuya Kyu, Daniel Sanz, Hasan Ahmed, Midushi Ghimire, Andrea Morrison-Porter, Hannah Quehl, Natalie S. Haddad, Weirong Chen, Suneethamma Cheedarla, Andrew S. Neish, John D. Roback, Rustom Antia, Jennifer Hom, Christopher M. Tipton, John M. Lindner, Eliver Ghosn, Surender Khurana, Christopher D. Scharer, Arezou Khosroshahi, F. Eun-Hyung Lee, Ignacio Sanz","doi":"10.1038/s41590-024-02010-9","DOIUrl":"10.1038/s41590-024-02010-9","url":null,"abstract":"Severe acute respiratory syndrome coronavirus 2 mRNA vaccination has reduced effectiveness in certain immunocompromised individuals. However, the cellular mechanisms underlying these defects, as well as the contribution of disease-induced cellular abnormalities, remain largely unexplored. In this study, we conducted a comprehensive serological and cellular analysis of patients with autoimmune systemic lupus erythematosus (SLE) who received the Wuhan-Hu-1 monovalent mRNA coronavirus disease 2019 vaccine. Our findings revealed that patients with SLE exhibited reduced avidity of anti-receptor-binding domain antibodies, leading to decreased neutralization potency and breadth. We also observed a sustained anti-spike response in IgD−CD27− ‘double-negative (DN)’ DN2/DN3 B cell populations persisting during memory responses and with greater representation in the SLE cohort. Additionally, patients with SLE displayed compromised anti-spike T cell immunity. Notably, low vaccine efficacy strongly correlated with higher values of a newly developed extrafollicular B and T cell score, supporting the importance of distinct B cell endotypes. Finally, we found that anti-BAFF blockade through belimumab treatment was associated with poor vaccine immunogenicity due to inhibition of naive B cell priming and an unexpected impact on circulating T follicular helper cells. SLE is a heterogeneous disorder that is characterized by different immune endotypes. Faliti et al. follow the immune memory responses upon mRNA COVID-19 vaccinations in a large cohort of patients with SLE. They note that skewed immune responses, such as lower seroconversion and neutralization, might be due to extrafollicular B and T cell biases in SLE endotypes.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"26 1","pages":"131-145"},"PeriodicalIF":27.7,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41590-024-02010-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142599626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune drivers of pain resolution and protection","authors":"Sara Hakim, Aakanksha Jain, Clifford J. Woolf","doi":"10.1038/s41590-024-02002-9","DOIUrl":"10.1038/s41590-024-02002-9","url":null,"abstract":"Immune cells are involved in the pathogenesis of pain by directly activating or sensitizing nociceptor sensory neurons. However, because the immune system also has the capacity to self-regulate through anti-inflammatory mechanisms that drive the resolution of inflammation, it might promote pain resolution and prevention. Here, we describe how immune cell-derived cytokines can act directly on sensory neurons to inhibit pain hypersensitivity and how immune-derived endogenous opioids promote analgesia. We also discuss how immune cells support healthy tissue innervation by clearing debris after nerve injury, protecting against axon retraction from target tissues and enhancing regeneration, preventing the development of chronic neuropathic pain. Finally, we review the accumulating evidence that manipulating immune activity positively alters somatosensation, albeit with currently unclear molecular and cellular mechanisms. Exploration of immune-mediated analgesia and pain prevention could, therefore, be important for the development of novel immune therapies for the treatment of clinical pain states. Woolf and colleagues review the current evidence that immune cells could promote pain resolution and prevention through direct effects on sensory neurons and through maintaining healthy tissue innervation.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"25 12","pages":"2200-2208"},"PeriodicalIF":27.7,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142598038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lactate fermentation intoxicates TILs","authors":"Brian G. Hunt, Emily Kessler, Nikhil S. Joshi","doi":"10.1038/s41590-024-02020-7","DOIUrl":"10.1038/s41590-024-02020-7","url":null,"abstract":"Tumor-infiltrating T cells are known to encounter chronic antigens and hypoxia, which results in exhaustion and dysfunction. New data show that lactate fermentation, a characteristic of solid tumors, promotes the uptake of lactate into T cells via the monocarboxylate transporter MCT11, which reduces the metabolic fitness and anti-tumor function of these cells, an effect that might be targeted by immunotherapy.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"25 12","pages":"2176-2177"},"PeriodicalIF":27.7,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142596854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dysfunction of exhausted T cells is enforced by MCT11-mediated lactate metabolism","authors":"Ronal M. Peralta, Bingxian Xie, Konstantinos Lontos, Hector Nieves-Rosado, Kellie Spahr, Supriya Joshi, B. Rhodes Ford, Kevin Quann, Andrew T. Frisch, Victoria Dean, Mary Philbin, Anthony R. Cillo, Sebastian Gingras, Amanda C. Poholek, Lawrence P. Kane, Dayana B. Rivadeneira, Greg M. Delgoffe","doi":"10.1038/s41590-024-01999-3","DOIUrl":"10.1038/s41590-024-01999-3","url":null,"abstract":"CD8+ T cells are critical mediators of antitumor immunity but differentiate into a dysfunctional state, known as T cell exhaustion, after persistent T cell receptor stimulation in the tumor microenvironment (TME). Exhausted T (Tex) cells are characterized by upregulation of coinhibitory molecules and reduced polyfunctionality. T cells in the TME experience an immunosuppressive metabolic environment via reduced levels of nutrients and oxygen and a buildup of lactic acid. Here we show that terminally Tex cells uniquely upregulate Slc16a11, which encodes monocarboxylate transporter 11 (MCT11). Conditional deletion of MCT11 in T cells reduced lactic acid uptake by Tex cells and improved their effector function. Targeting MCT11 with an antibody reduced lactate uptake specifically in Tex cells, which, when used therapeutically in tumor-bearing mice, resulted in reduced tumor growth. These data support a model in which Tex cells upregulate MCT11, rendering them sensitive to lactic acid present at high levels in the TME. Here the authors show that high expression of MCT11 is key to the dysfunctionality associated with exhausted CD8+ T cells in tumors. By targeting MCT11, uptake of lactic acid, which is abundant in the tumor, is reduced, resulting in improved effector functions and tumor immunity.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"25 12","pages":"2297-2307"},"PeriodicalIF":27.7,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41590-024-01999-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142596855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanotech unveils cytokine traces in post-COVID cardiovascular complications","authors":"Harish Narasimhan, Jie Sun","doi":"10.1038/s41590-024-02017-2","DOIUrl":"10.1038/s41590-024-02017-2","url":null,"abstract":"Trace levels of circulating cytokines correlate with the prevalence of cardiovascular symptoms following COVID-19.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"25 12","pages":"2178-2179"},"PeriodicalIF":27.7,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142596853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}