Nature Immunology最新文献

GFI1-driven transcriptional and epigenetic programs maintain CD8+ T cell stemness and persistence gfi1驱动的转录和表观遗传程序维持CD8+ T细胞的干性和持久性

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-05-15 DOI: 10.1038/s41590-025-02151-5

M. Zeeshan Chaudhry, Evelyn Chen, Hiu On Man, Aneesha Jones, Renae Denman, Huiyang Yu, Qiutong Huang, Adrian Ilich, Jaring Schreuder, Severine Navarro, Zewen K. Tuong, Gabrielle T. Belz

{"title":"GFI1-driven transcriptional and epigenetic programs maintain CD8+ T cell stemness and persistence","authors":"M. Zeeshan Chaudhry, Evelyn Chen, Hiu On Man, Aneesha Jones, Renae Denman, Huiyang Yu, Qiutong Huang, Adrian Ilich, Jaring Schreuder, Severine Navarro, Zewen K. Tuong, Gabrielle T. Belz","doi":"10.1038/s41590-025-02151-5","DOIUrl":"https://doi.org/10.1038/s41590-025-02151-5","url":null,"abstract":"Long-lived memory CD8+ T cells are essential for the control of persistent viral infections. The mechanisms that preserve memory cells are poorly understood. Fate mapping of the transcriptional repressor GFI1 identified that GFI1 was differentially regulated in virus-specific CD8+ T cells and was selectively expressed in stem cell memory and central memory cells. Deletion of GFI1 led to reduced proliferation and progressive loss of memory T cells, which in turn resulted in failure to maintain antigen-specific CD8+ T cell populations following infection with chronic lymphocytic choriomeningitis virus or murine cytomegalovirus. Ablation of GFI1 resulted in downregulation of the transcription factors EOMES and BCL-2 in memory CD8+ T cells. Ectopic expression of EOMES rescued the expression of BCL-2, but the persistence of memory CD8+ T cells was only partially rescued. These findings highlight the critical role of GFI1 in the long-term maintenance of memory CD8+ T cells in persistent infections by sustaining their proliferative potential.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"20 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979579","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}

引用次数: 0

Mucosal unadjuvanted booster vaccines elicit local IgA responses by conversion of pre-existing immunity in mice 粘膜无佐剂加强疫苗通过转化小鼠已有免疫引起局部IgA反应

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-05-13 DOI: 10.1038/s41590-025-02156-0

Dong-il Kwon, Tianyang Mao, Benjamin Israelow, Keyla Santos Guedes de Sá, Huiping Dong, Akiko Iwasaki

{"title":"Mucosal unadjuvanted booster vaccines elicit local IgA responses by conversion of pre-existing immunity in mice","authors":"Dong-il Kwon, Tianyang Mao, Benjamin Israelow, Keyla Santos Guedes de Sá, Huiping Dong, Akiko Iwasaki","doi":"10.1038/s41590-025-02156-0","DOIUrl":"https://doi.org/10.1038/s41590-025-02156-0","url":null,"abstract":"Mucosal delivery of vaccine boosters induces robust local protective immune responses even without any adjuvants. Yet, the mechanisms by which antigen alone induces mucosal immunity in the respiratory tract remain unclear. Here we show that an intranasal booster with an unadjuvanted recombinant SARS-CoV-2 spike protein, after intramuscular immunization with 1 μg of mRNA–LNP vaccine encoding the full-length SARS-CoV-2 spike protein (Pfizer/BioNTech BNT162b2), elicits protective mucosal immunity by retooling the lymph node-resident immune cells. On intranasal boosting, peripheral lymph node-primed B cells rapidly migrated to the lung through CXCR3–CXCL9 and CXCR3–CXCL10 signaling and differentiated into antigen-specific IgA-secreting plasma cells. Memory CD4+ T cells in the lung served as a natural adjuvant for developing mucosal IgA by inducing the expression of chemokines CXCL9 and CXCL10 for memory B cell recruitment. Furthermore, CD40 and TGFβ signaling had important roles in mucosal IgA development. Repeated mucosal boosting with an unadjuvanted protein amplified anamnestic IgA responses in both the upper and the lower respiratory tracts. These findings help explain why nasal boosters do not require an adjuvant to induce robust mucosal immunity at the respiratory mucosa and can be used to design safe and effective vaccines against respiratory pathogens.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"41 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143940152","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}

引用次数: 0

Inhibition of ENT1 relieves intracellular adenosine-mediated T cell suppression in cancer 抑制ENT1可缓解肿瘤细胞内腺苷介导的T细胞抑制

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-05-12 DOI: 10.1038/s41590-025-02153-3

Theodore J. Sanders, Christopher S. Nabel, Margreet Brouwer, Annelise L. Hermant, Lucas Chaible, Jean-Philippe Deglasse, Nicolas Rosewick, Angélique Pabois, Wilfried Cathou, Aurore Smets, Michael Deligny, João Marchante, Quentin Dubray, Marie-Claire Letellier, Chiara Martinoli, Reece Marillier, Olivier De Henau, Yvonne McGrath, Matthew G. Vander Heiden, Erica Houthuys

{"title":"Inhibition of ENT1 relieves intracellular adenosine-mediated T cell suppression in cancer","authors":"Theodore J. Sanders, Christopher S. Nabel, Margreet Brouwer, Annelise L. Hermant, Lucas Chaible, Jean-Philippe Deglasse, Nicolas Rosewick, Angélique Pabois, Wilfried Cathou, Aurore Smets, Michael Deligny, João Marchante, Quentin Dubray, Marie-Claire Letellier, Chiara Martinoli, Reece Marillier, Olivier De Henau, Yvonne McGrath, Matthew G. Vander Heiden, Erica Houthuys","doi":"10.1038/s41590-025-02153-3","DOIUrl":"https://doi.org/10.1038/s41590-025-02153-3","url":null,"abstract":"The benefit of immune checkpoint blockade for cancer therapy is limited to subsets of patients because of factors including the accumulation of immunosuppressive metabolites, such as adenosine, within tumors. Pharmacological inhibition of adenosine generation and signaling is an active area of clinical investigation, but only limited clinical benefit has been reported. Here, we show that adenosine suppresses anti-cancer T cell responses following uptake into activated T cells by equilibrative nucleoside transporter 1 (ENT1) and inhibition of de novo pyrimidine nucleotide synthesis. We identify EOS301984 as a potent ENT1 antagonist that restores pyrimidine levels in activated T cells in adenosine-rich environments, resulting in enhanced tumor cell killing by memory T cells and increased ex vivo expansion of functional human tumor-infiltrating lymphocytes. A combination of EOS301984 with anti-PD-1 led to synergistic control of tumor growth in a humanized mouse model of triple-negative breast cancer. ENT1 inhibition, therefore, augments anti-cancer immune responses through the restoration of pyrimidine nucleotide synthesis in T cells suppressed by adenosine.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"10 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143933224","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}

引用次数: 0

Cutaneous T cell immunity 皮肤T细胞免疫

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-05-07 DOI: 10.1038/s41590-025-02145-3

Pirooz Zareie, Eric S. Weiss, Daniel H. Kaplan, Laura K. Mackay

引用次数: 0

Immune–epithelial–stromal networks define the cellular ecosystem of the small intestine in celiac disease 免疫-上皮-基质网络定义了腹腔疾病小肠的细胞生态系统

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-05-06 DOI: 10.1038/s41590-025-02146-2

Michael E. B. FitzPatrick, Agne Antanaviciute, Melanie Dunstan, Karolina Künnapuu, Dominik Trzupek, Nicholas M. Provine, Kyla Dooley, Jia-Yuan Zhang, Sophie L. Irwin, Lucy C. Garner, Jane I. Pernes, Ricardo C. Ferreira, Sarah C. Sasson, Dominik Aschenbrenner, Devika Agarwal, Astor Rodrigues, Lucy Howarth, Oliver Brain, Darren Ruane, Elizabeth Soilleux, Sarah A. Teichmann, Calliope A. Dendrou, Alison Simmons, Holm H. Uhlig, John A. Todd, Paul Klenerman

{"title":"Immune–epithelial–stromal networks define the cellular ecosystem of the small intestine in celiac disease","authors":"Michael E. B. FitzPatrick, Agne Antanaviciute, Melanie Dunstan, Karolina Künnapuu, Dominik Trzupek, Nicholas M. Provine, Kyla Dooley, Jia-Yuan Zhang, Sophie L. Irwin, Lucy C. Garner, Jane I. Pernes, Ricardo C. Ferreira, Sarah C. Sasson, Dominik Aschenbrenner, Devika Agarwal, Astor Rodrigues, Lucy Howarth, Oliver Brain, Darren Ruane, Elizabeth Soilleux, Sarah A. Teichmann, Calliope A. Dendrou, Alison Simmons, Holm H. Uhlig, John A. Todd, Paul Klenerman","doi":"10.1038/s41590-025-02146-2","DOIUrl":"https://doi.org/10.1038/s41590-025-02146-2","url":null,"abstract":"The immune–epithelial–stromal interactions underpinning intestinal damage in celiac disease (CD) are incompletely understood. To address this, we performed single-cell transcriptomics (RNA sequencing; 86,442 immune, parenchymal and epithelial cells; 35 participants) and spatial transcriptomics (20 participants) on CD intestinal biopsy samples. Here we show that in CD, epithelial populations shifted toward a progenitor state, with interferon-driven transcriptional responses, and perturbation of secretory and enteroendocrine populations. Mucosal T cells showed numeric and functional changes in regulatory and follicular helper-like CD4+ T cells, intraepithelial lymphocytes, CD8+ and γδ T cell subsets, with skewed T cell antigen receptor repertoires. Mucosal changes remained detectable despite treatment, representing a persistent immune–epithelial ‘scar’. Spatial transcriptomics defined transcriptional niches beyond those captured in conventional histological scores, including CD-specific lymphoid aggregates containing T cell–B cell interactions. Receptor–ligand spatial analyses integrated with disease susceptibility gene expression defined networks of altered chemokine and morphogen signaling, and provide potential therapeutic targets for CD prevention and treatment.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"25 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143909959","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}

引用次数: 0

IgA clears gut viruses IgA清除肠道病毒

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-04-30 DOI: 10.1038/s41590-025-02159-x

Paula Jauregui

{"title":"IgA clears gut viruses","authors":"Paula Jauregui","doi":"10.1038/s41590-025-02159-x","DOIUrl":"https://doi.org/10.1038/s41590-025-02159-x","url":null,"abstract":"Secretory IgA coats the intestinal microbiota and is the most abundant antibody isotype produced in the mammalian gastrointestinal mucosa. In Cell Host and Microbe, Lisicka et al. show that IgA prevents chronic gut colonization by viruses and that IgA deficiency in some individuals increases susceptibility to colitis if exposed to viral pathobionts. The authors designed a mouse model of secretory IgA deficiency to demonstrate that IgA mediates regulation of the microbiota by preventing the expansion of antigen-driven CD8αβ+ intraepithelial lymphocytes (IELs) primed by type 1 conventional dendritic cells (cDC1). Using germ-free mice and colonizing them with fecal filtrate from their mouse model, the authors conclude that murine astrovirus (MuAstV) drives CD8αβ+ IELs in IgA-deficient mice, which are not able to clear the virus, but can maintain homeostasis. The authors show that IgA derived from the germinal center plasma cells regulates the colonization of specific RNA viruses in the small intestine and limits the expansion of CD8αβ+ T cells. Using diverse mouse models for colitis, they conclude that in genetically susceptible mice, IgA deficiency combined with the presence of murine norovirus increases susceptibility to colitis.Original reference: Cell Host Microbe 33, 498–511.e10 (2025)","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"25 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893160","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}

引用次数: 0

Treg cells control female nociception Treg细胞控制女性的伤害感觉

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-04-30 DOI: 10.1038/s41590-025-02160-4

Stephanie Houston

{"title":"Treg cells control female nociception","authors":"Stephanie Houston","doi":"10.1038/s41590-025-02160-4","DOIUrl":"https://doi.org/10.1038/s41590-025-02160-4","url":null,"abstract":"Women experience a higher prevalence of chronic pain, and pain hypersensitivity has been observed in female mice, but that mechanisms that drive sexual dimorphism in nociception remain unclear. In Science, Midavaine et al. find that meningeal regulatory T (mTreg) cells controlled the responses of female mice to mechanical pain via the endogenous opioid peptide enkephalin. Intrathecal injection of pegylated diphtheria toxin to Foxp3-DTR mice enabled the selective depletion of mTreg cells, which resulted in decreased mechanical nociceptive thresholds in female, but not male mice. Conversely, intrathecal injection of low-dose IL-2 led to mTreg cell expansion, and this increased the nociceptive threshold in female, but not male mice. Blocking female sex hormones prevented the mTreg cell expansion-mediated increases in the nociceptive threshold. mTreg cells expressed Penk, which encodes proenkephalin, a precursor of analgesic enkephalin peptides. In female mic, the expansion of mTreg cells resulted in increased levels of enkephalin in the cerebrospinal fluid. During nerve injury, enkephalin decreased pain sensing by activating δ-opioid receptors expressed by sensory neurons. Thus, in female mice, mTreg cells have an important role in controlling the activation of sensory neurons in response to mechanical pain.Original reference: Science https://doi.org/10.1126/science.adq6531 (2025)","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"45 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893164","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}

引用次数: 0

Skin–gut crosstalk

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-04-30 DOI: 10.1038/s41590-025-02158-y

Nicholas J. Bernard

{"title":"Skin–gut crosstalk","authors":"Nicholas J. Bernard","doi":"10.1038/s41590-025-02158-y","DOIUrl":"https://doi.org/10.1038/s41590-025-02158-y","url":null,"abstract":"Skin damage can have systemic effects but whether it can result in the priming of immune responses that are spatially removed from the skin is less clear. Data now published in Science Immunology show that cytokines released from damaged skin can function as endocrine adjuvants to prime normally tolerogenic gastrointestinal immune responses to the model food antigen ovalbumin, thereby driving humoral responses in mice. This ‘remote priming’ was demonstrated by oral gavage of ovalbumin in combination with tape stripping to damage the skin and resulted in ovalbumin-specific antibody responses. The same allergic sensitization was shown by two other means of acute skin damage (punch biopsy or intradermal acetone injection), a model of chronic atopic dermatitis (using calcipotriol) and in response to ultraviolet radiation damage. Although the cytokine signatures varied with the different skin damage methods, the researchers used cytokine immunizations and various cell-specific knockout mice to show that the cytokines IL-33 and TSLP were sufficient to drive similar ovalbumin-specific antibody responses to skin damage, in part by activation of group 2 innate lymphoid cells.Original reference: Sci. Immunol. 10, eadn0688 (2025)","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"16 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893197","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}

引用次数: 0

Gut T cell plasticity generates pathogenic TFH cells that promote systemic autoimmunity 肠道T细胞可塑性产生致病性TFH细胞，促进全身自身免疫

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-04-30 DOI: 10.1038/s41590-025-02147-1

引用次数: 0

Identification of soluble biomarkers that associate with distinct manifestations of long COVID 与新冠肺炎不同表现相关的可溶性生物标志物的鉴定

IF 30.5 1区医学

Nature Immunology Pub Date : 2025-04-30 DOI: 10.1038/s41590-025-02135-5

Yu Gao, Curtis Cai, Sarah Adamo, Elsa Biteus, Habiba Kamal, Lena Dager, Kelly L. Miners, Sian Llewellyn-Lacey, Kristin Ladell, Pragati S. Amratia, Kirsten Bentley, Simon Kollnberger, Jinghua Wu, Mily Akhirunnesa, Samantha A. Jones, Per Julin, Christer Lidman, Richard J. Stanton, Paul A. Goepfert, Michael J. Peluso, Steven G. Deeks, Helen E. Davies, Soo Aleman, Marcus Buggert, David A. Price

{"title":"Identification of soluble biomarkers that associate with distinct manifestations of long COVID","authors":"Yu Gao, Curtis Cai, Sarah Adamo, Elsa Biteus, Habiba Kamal, Lena Dager, Kelly L. Miners, Sian Llewellyn-Lacey, Kristin Ladell, Pragati S. Amratia, Kirsten Bentley, Simon Kollnberger, Jinghua Wu, Mily Akhirunnesa, Samantha A. Jones, Per Julin, Christer Lidman, Richard J. Stanton, Paul A. Goepfert, Michael J. Peluso, Steven G. Deeks, Helen E. Davies, Soo Aleman, Marcus Buggert, David A. Price","doi":"10.1038/s41590-025-02135-5","DOIUrl":"https://doi.org/10.1038/s41590-025-02135-5","url":null,"abstract":"Long coronavirus disease (COVID) is a heterogeneous clinical condition of uncertain etiology triggered by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we used ultrasensitive approaches to profile the immune system and the plasma proteome in healthy convalescent individuals and individuals with long COVID, spanning geographically independent cohorts from Sweden and the United Kingdom. Symptomatic disease was not consistently associated with quantitative differences in immune cell lineage composition or antiviral T cell immunity. Healthy convalescent individuals nonetheless exhibited higher titers of neutralizing antibodies against SARS-CoV-2 than individuals with long COVID, and extensive phenotypic analyses revealed a subtle increase in the expression of some co-inhibitory receptors, most notably PD-1 and TIM-3, among SARS-CoV-2 nonspike-specific CD8+ T cells in individuals with long COVID. We further identified a shared plasma biomarker signature of disease linking breathlessness with apoptotic inflammatory networks centered on various proteins, including CCL3, CD40, IKBKG, IL-18 and IRAK1, and dysregulated pathways associated with cell cycle progression, lung injury and platelet activation, which could potentially inform the diagnosis and treatment of long COVID.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"195 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893198","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}

引用次数: 0