ImmunityPub Date : 2026-09-08Epub Date: 2026-07-17DOI: 10.1016/j.immuni.2026.06.020
Kathryn A Jacobs, Yichao Hua, Apostolos Panagiotis Nikolakopoulos, Swati Gupta, Gerlanda Vella, Ana Filipa Domingues Laranjeiro, Julie Bonnereau, Mélanie Guyot, Maria Livia Sassano, Larissa Mourao, Feyza Cansiz, Gabriele Allies, Nicolas Van Baren, Sophie Lucas, Hiroto Kawashima, Wiebke Sondermann, Florian Rambow, Alpaslan Tasdogan, Colinda Scheele, Patrizia Agostinis, Gabriele Bergers
{"title":"Autophagy maintains high endothelial venule identity and function during inflammation.","authors":"Kathryn A Jacobs, Yichao Hua, Apostolos Panagiotis Nikolakopoulos, Swati Gupta, Gerlanda Vella, Ana Filipa Domingues Laranjeiro, Julie Bonnereau, Mélanie Guyot, Maria Livia Sassano, Larissa Mourao, Feyza Cansiz, Gabriele Allies, Nicolas Van Baren, Sophie Lucas, Hiroto Kawashima, Wiebke Sondermann, Florian Rambow, Alpaslan Tasdogan, Colinda Scheele, Patrizia Agostinis, Gabriele Bergers","doi":"10.1016/j.immuni.2026.06.020","DOIUrl":"10.1016/j.immuni.2026.06.020","url":null,"abstract":"<p><p>High endothelial venules (HEVs) play a crucial role in adaptive immune responses in secondary lymphoid organs (SLOs). They are equipped with high amounts of peripheral node addressin (PNAd), harboring carbohydrate structures that serve as L-selectin ligands to efficiently facilitate lymphocyte homing. During inflammation, the HEV network expands in SLOs, increasing lymphocyte infiltration, but the underlying mechanisms that maintain HEVs remain underexplored. Here, we report that autophagy is essential for HEV function and expansion. Using single-cell transcriptomics, unbiased proteomics, intravital imaging, and an inducible HEV tracer system in mice, we demonstrate that autophagy deficiency compromises lymphotoxin beta receptor (LTβR) signaling and the unfolded protein response in HEVs, leading to disrupted PNAd production, dedifferentiation, and reduced lymphocyte homing. Autophagy deficiency and LTβR blockade impair HEV function and reduce skin inflammation in psoriasis-affected mice by limiting immune infiltration and cytokine release. Our work reveals that autophagy safeguards HEV identity and function during inflammation.</p>","PeriodicalId":13269,"journal":{"name":"Immunity","volume":" ","pages":"2429-2446.e8"},"PeriodicalIF":30.6,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13574368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148470055","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}
ImmunityPub Date : 2026-09-08Epub Date: 2026-07-15DOI: 10.1016/j.immuni.2026.06.005
Rintaro Shibuya, Nobuya Abe, Keaton Song, Nathan D Rossen, Masato Tamari, Zhen Wang, Zili Xie, Yuki Abe, Hisato Iriki, Ayana Iijima, Lydia Zamidar, Xu Li, Xia Meng, Andras Bimbo-Szuhai, Veronica Burstein, Jill K Gregory, Natalia P Biscola, Karen Anthony, Michel Enamorado, Steven J Van Dyken, Kenji Kabashima, Hongzhen Hu, Brian S Kim
{"title":"Activation of the auricular vagus nerve reflex suppresses airway inflammation.","authors":"Rintaro Shibuya, Nobuya Abe, Keaton Song, Nathan D Rossen, Masato Tamari, Zhen Wang, Zili Xie, Yuki Abe, Hisato Iriki, Ayana Iijima, Lydia Zamidar, Xu Li, Xia Meng, Andras Bimbo-Szuhai, Veronica Burstein, Jill K Gregory, Natalia P Biscola, Karen Anthony, Michel Enamorado, Steven J Van Dyken, Kenji Kabashima, Hongzhen Hu, Brian S Kim","doi":"10.1016/j.immuni.2026.06.005","DOIUrl":"10.1016/j.immuni.2026.06.005","url":null,"abstract":"<p><p>The vagus nerve regulates inflammation via sensory-motor arcs. While vagal sensory neurons relay signals from within the body (interoception), whether external inputs can regulate visceral neuroimmune responses (exteroception) remains poorly understood. We unveiled a skin-lung reflex by which sensory neurons from the auricular skin suppressed Alternaria alternata-induced allergic airway inflammation. Viral and chemical neural tracing revealed distinct sensory projections from the vagal ganglia to the auricular skin. Pharmacologic, chemogenetic, and optogenetic activation of auricular transient receptor potential vanilloid 1 (TRPV1)<sup>+</sup> afferents attenuated type 2 allergic lung inflammation, including group 2 innate lymphoid cell, eosinophil, and type 2 cytokine responses in the airway. Conversely, silencing of these sensory neurons via the skin exacerbated lung inflammation, and immunosuppression of airway inflammation was dependent on the neuropeptide calcitonin gene-related peptide (CGRP)β. These findings reveal an evolutionarily conserved somato-visceral reflex by which exteroceptive inputs impact visceral inflammation. Thus, transcutaneous neuromodulation may represent a therapeutic strategy to treat visceral inflammation.</p>","PeriodicalId":13269,"journal":{"name":"Immunity","volume":" ","pages":"2402-2412.e6"},"PeriodicalIF":30.6,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148455706","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":"Flavin adenine dinucleotide is an endogenous suppressor for cytosolic DNA and RNA sensors to modulate innate immunity.","authors":"Yao Wang, Yanyan Shen, Jiayu Liu, Qi Qi, Yue Guo, Yunying Wang, Boyang Xie, Chunyan Yan, Yanhong Liu, Zhi Jin, Ruibo Wang, Aiping Cao, Juncheng Li, Zengqing Song, Jing Chen, Qiuying Han, Yingjie Zhu, Kun Zhang, Taixia Wang, Tao Li, Xin Pan, Xinhua He, Tao Zhou, Ailing Li, Xuemin Zhang, Na Wang, Qing Xia, Weina Zhang","doi":"10.1016/j.immuni.2026.06.010","DOIUrl":"10.1016/j.immuni.2026.06.010","url":null,"abstract":"<p><p>Cytosolic DNA and RNA sensing is crucial for innate immunity, playing essential roles in pathogen defense and autoinflammation induction. We reported the endogenous metabolite flavin adenine dinucleotide (FAD) as a molecular brake restraining both cytosolic DNA and RNA sensing. It bound directly to cytosolic nucleic acid sensors cyclic GMP-AMP synthase (cGAS) and retinoic acid-inducible gene I (RIG-I), occupying catalytic pockets to suppress their activity and downstream immune responses. Physiologically, FAD prevented self-nucleic acid-induced sterile inflammation and maintained immune homeostasis. FAD deficiency due to FAD synthase (FLAD1) ablation exacerbated auto-inflammation and cellular senescence. Upon viral infection, reduced FLAD1 activity lowered FAD amounts, which removed its inhibitory control over DNA and RNA sensors, thus facilitating extensive interferon-I (IFN-I) signaling activation. Consequently, FLAD1 depletion strengthened the innate immune response and protected mice from viral infection. Our findings identify FAD as a natural suppressor of both cytosolic DNA and RNA sensing, offering therapeutic potential for inflammatory diseases.</p>","PeriodicalId":13269,"journal":{"name":"Immunity","volume":" ","pages":"2413-2428.e9"},"PeriodicalIF":30.6,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148436490","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}
ImmunityPub Date : 2026-09-08Epub Date: 2026-08-11DOI: 10.1016/j.immuni.2026.07.014
Yuhan Bi, Kevin Brulois, Aiman Ayesha, Menglan Xiang, Romain Ballet, Borja Ocón, Theresa Dinh, Nicole Lazarus, Manali Kunte, Griselda Ramos, Florea Lupu, Jonathan H Lin, Eugene C Butcher, Junliang Pan
{"title":"Coordinated transcriptional networks program organelle expansion and metabolic flows for high endothelial morphology and function.","authors":"Yuhan Bi, Kevin Brulois, Aiman Ayesha, Menglan Xiang, Romain Ballet, Borja Ocón, Theresa Dinh, Nicole Lazarus, Manali Kunte, Griselda Ramos, Florea Lupu, Jonathan H Lin, Eugene C Butcher, Junliang Pan","doi":"10.1016/j.immuni.2026.07.014","DOIUrl":"10.1016/j.immuni.2026.07.014","url":null,"abstract":"<p><p>High endothelial cells (HECs) control lymphocyte homing for adaptive immunity. They are defined by plump morphology, reflecting endoplasmic reticulum (ER) and Golgi expansion, and are by display of sulfo-sialomucins of the peripheral node addressin (PNAd) critical for lymphocyte recruitment. How these features are linked was unclear. Here, we found that HEC genes for sulfoglycoprotein synthesis and organelle expansion are enriched in binding motifs for ER stress-response transcription factors XBP1 and CREB3L2. These factors bound and drove expression from conserved elements in sulfo- and fucosyl-transferase and transporter genes for PNAd synthesis. Endothelial-specific deletion of Xbp1, or pharmacologic inhibition of enzymes for XBP1 or CREB3L2 activation, impaired PNAd expression, flattened HECs, reduced lymphocyte recruitment, and prevented HEC induction during inflammation. Parallel programs were found in intestinal goblet cells, suggesting conserved mechanisms coupling organelle scaling with sulfoglycoprotein production. Thus, HECs employ adaptive ER programs to build the biosynthetic infrastructure driving their morphology and function.</p>","PeriodicalId":13269,"journal":{"name":"Immunity","volume":" ","pages":"2447-2464.e6"},"PeriodicalIF":30.6,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148712218","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}
ImmunityPub Date : 2026-09-08Epub Date: 2026-08-28DOI: 10.1016/j.immuni.2026.08.003
Matthew Fish, Jennifer Rynne, Emma Timms, Aislinn Jennings, Carolynn Lam, Gill Arbane, Neus Novellas, Sara Campos, Barney Sanderson, Paolo Bosco, Gianluca Lucchese, Richard Ellis, Cynthia Bishop, Katrina Todd, Yasmeen Ghnewa, Mervyn Singer, Chad Swanson, Manu Shankar-Hari
{"title":"Temporal analyses of immune responses in sepsis reveal asynchrony between clinical stage of illness and immune states.","authors":"Matthew Fish, Jennifer Rynne, Emma Timms, Aislinn Jennings, Carolynn Lam, Gill Arbane, Neus Novellas, Sara Campos, Barney Sanderson, Paolo Bosco, Gianluca Lucchese, Richard Ellis, Cynthia Bishop, Katrina Todd, Yasmeen Ghnewa, Mervyn Singer, Chad Swanson, Manu Shankar-Hari","doi":"10.1016/j.immuni.2026.08.003","DOIUrl":"10.1016/j.immuni.2026.08.003","url":null,"abstract":"<p><p>Deeper understanding of the temporal immune response architecture in sepsis may enable effective therapeutic interventions. Here, we investigated longitudinal immune response programs in critically ill patients with sepsis, as compared with elective cardiac surgery patients. Although transcriptomic profiles obtained at four clinical time points between admission and recovery or death showed substantial overlap, pseudotime analysis revealed a trajectory comprising three sepsis temporal immune states (STImS1-3). Weighted gene co-expression network analysis and immunophenotypic and cytokine profiles identified distinct programs associated with each STImS, and corresponding hub genes mapped to putative immunomodulatory targets, including interleukin 6 blockade, iron chelation, and anthracyclines. STImS1 was characterized by the strongest innate immune responses, elevated resistance programs, variable disease tolerance programs, and enrichment of low-resilience features, including mortality-associated signatures. In contrast, STImS3 was enriched for adaptive immune responses. Thus, clinical time and immune response trajectory are partially decoupled in sepsis, illustrating the need to align therapeutic intervention with the temporal immune state in sepsis.</p>","PeriodicalId":13269,"journal":{"name":"Immunity","volume":" ","pages":"2580-2598.e7"},"PeriodicalIF":30.6,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148850373","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}
ImmunityPub Date : 2026-09-08DOI: 10.1016/j.immuni.2026.08.007
Aditya Patil,Lloyd Bod
{"title":"Sensory nerves send lymphoid assembly up in smoke","authors":"Aditya Patil,Lloyd Bod","doi":"10.1016/j.immuni.2026.08.007","DOIUrl":"https://doi.org/10.1016/j.immuni.2026.08.007","url":null,"abstract":"Accumulating evidence implicates sensory neurons in tumor progression, but signals linking nociceptive activity to impaired antitumor immunity remain unclear. In a recent issue of Cell, Ho et al. show that nociceptor activation impedes TLS assembly through CGRP, and cigarette smoke engages this neuroimmune axis, promoting tumor growth independently of mutagenic effects.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"20 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148902546","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}
ImmunityPub Date : 2026-09-08Epub Date: 2026-07-17DOI: 10.1016/j.immuni.2026.06.022
Petros Tzerpos, Dóra Bojcsuk, Krisztian Bene, Noemí Caballero-Sánchez, Zofia Parteka-Tojek, Krzysztof Banecki, Sevastianos Korsak, Sarah M Pritchett, Andreas Patsalos, Darby Oleksak, Wilhelm K Berger, Michalis E Sarris, Nikolaos Giannakis, Sophie Chantalat, Timea Cseh, Evangelia K Papachristou, Ferenc Erdélyi, Zoltán Máté, Gabor Szabo, Gergely Nagy, Jason S Carroll, Charalampos G Spilianakis, John W R Schwabe, Dariusz Plewczynski, Laszlo Nagy
{"title":"The transcription factor BACH1 couples chromatin priming and repression to enable macrophage plasticity and adaptation.","authors":"Petros Tzerpos, Dóra Bojcsuk, Krisztian Bene, Noemí Caballero-Sánchez, Zofia Parteka-Tojek, Krzysztof Banecki, Sevastianos Korsak, Sarah M Pritchett, Andreas Patsalos, Darby Oleksak, Wilhelm K Berger, Michalis E Sarris, Nikolaos Giannakis, Sophie Chantalat, Timea Cseh, Evangelia K Papachristou, Ferenc Erdélyi, Zoltán Máté, Gabor Szabo, Gergely Nagy, Jason S Carroll, Charalampos G Spilianakis, John W R Schwabe, Dariusz Plewczynski, Laszlo Nagy","doi":"10.1016/j.immuni.2026.06.022","DOIUrl":"10.1016/j.immuni.2026.06.022","url":null,"abstract":"<p><p>Macrophage activation and tissue adaptation involve precise transcriptional control by lineage-determining transcription factors (LDTFs) and stimulus-dependent TFs. The heme-regulated transcriptional repressor BACH1 clusters with myeloid LDTFs in unstimulated macrophages, suggesting a role in shaping macrophage identity and function. We found that BACH1 bound to both inactive and active regulatory regions, including latent enhancers. BACH1 recruited the NuRD complex and had dual functions, establishing early chromatin accessibility while actively repressing transcription. Upon inflammatory stimulation, BACH1 rapidly redistributed in cis to nearby promoters, reshaping chromatin occupancy, motif specificity, and enhancer-promoter interactions. BACH1 constrained 3D chromatin architecture, limiting enhancer mobility and TF complex dynamics. In vivo, Bach1 deletion impaired macrophage polarization and tissue adaptation and limited resilience during systemic and regenerative inflammation. Thus, BACH1 acts as an early chromatin accessibility-priming factor while actively repressing transcription-a regulatory activity that can be defined as pioneer repression-thereby shaping the macrophage epigenome in response to inflammatory and tissue contexts.</p>","PeriodicalId":13269,"journal":{"name":"Immunity","volume":" ","pages":"2465-2482.e8"},"PeriodicalIF":30.6,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148470065","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}
ImmunityPub Date : 2026-09-08DOI: 10.1016/j.immuni.2026.08.010
Joshua McKeever,Andrew S. Koh
{"title":"Chromatin triggers tissue-specific immunity in 3D","authors":"Joshua McKeever,Andrew S. Koh","doi":"10.1016/j.immuni.2026.08.010","DOIUrl":"https://doi.org/10.1016/j.immuni.2026.08.010","url":null,"abstract":"Antigenic and environmental stimuli sensed by innate and adaptive immune cells trigger cognate functions that allow the coordination of the appropriate immune response. In this issue of Immunity, Tzerpos et al. and Jay et al. demonstrate that chromatin architecture dynamics integrate sensory inputs with functional outputs to regulate and direct immune cell responses.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"2 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148902464","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":"A pulmonary innate lymphoid cell-driven serotonergic neuroimmune axis orchestrates airway hyperreactivity and cough hypersensitivity","authors":"Chia-Hui Luo,Jheng-Syuan Shao,Alan Chuan-Ying Lai,Wei-Chang Huang,Ko-Chien Wu,Wei-Yu Chen,Chih-Cheng Chen,Nicholas W. Lukacs,Ya-Jen Chang","doi":"10.1016/j.immuni.2026.08.004","DOIUrl":"https://doi.org/10.1016/j.immuni.2026.08.004","url":null,"abstract":"Asthma is a heterogeneous disease characterized by airway hyperreactivity (AHR) and chronic cough, exacerbated by respiratory viruses or allergen exposure. Yet, the immune pathway-mediated serotonergic circuits underlying these responses remain poorly defined. Here, we identified a serotonergic neuroimmune axis in which pulmonary group 2 innate lymphoid cells (ILC2s) expressed tryptophan hydroxylase-1 (Tph1) and released serotonin via CCAAT/enhancer-binding protein beta (C/EBPβ)-dependent transcription following interleukin (IL)-33 stimulation. Tph1 deficiency in ILC2s and adoptive transfer experiments demonstrated that ILC2-derived serotonin amplified type 2 cytokine production via 5-hydroxytryptamine (5-HT)2A-NF-κB activation, resulting in exacerbated AHR in respiratory syncytial virus-driven asthmatic models. Using engineered viral tools, we showed that ILC2-derived serotonin sensitized vagal sensory neurons through 5-HT3A to promote cough hypersensitivity. Clinically, asthma patients exhibited elevated TPH1 and plasma serotonin levels, both of which correlated with type 2 cytokines. Together, these findings reveal that an ILC2-driven serotonergic circuit contributes to asthma pathophysiology and highlight serotonergic signaling as a therapeutic target.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"34 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148899074","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":"Twenty-year persistence of SARS-CoV-1 immune imprinting shapes antibody responses to SARS-CoV-2 infection","authors":"Qi Zhang,Peng Chen,Fenglin Guo,Runhong Zhou,Ruihan Guo,Xiaofei Ge,Qianqian Yang,Xin Xie,Wei Xia,Junping Fan,Ziqing Yang,Yan Xu,Huiyu Huang,Jinqian Li,Han Wang,Huiyu Liao,Xuanling Shi,Na Liu,Yuting Chen,Zhiwei Chen,Jianzhu Ma,Xinquan Wang,Tong Zhang,Linqi Zhang","doi":"10.1016/j.immuni.2026.08.009","DOIUrl":"https://doi.org/10.1016/j.immuni.2026.08.009","url":null,"abstract":"Antibody imprinting is well recognized, yet its long-term dynamics and epitope specificity remain poorly understood. Here, we studied individuals sequentially infected with SARS-CoV-1 (SARS-1) and SARS-CoV-2 (SARS-2) over two decades and found durable imprinting of antibody responses following SARS-2 BF.7 breakthrough infection. Approximately 60% of isolated monoclonal antibodies were SARS-1 imprinted and targeted conserved receptor-binding domain regions, whereas 37% overcame imprinting to recognize the SARS-2 receptor-binding motif overlapping the ACE2-binding site. Notably, some SARS-1-only antibodies retained germline-like features and neutralizing activity 20 years after infection. One exceptionally imprinted broadly neutralizing antibody, THZ937, protected hamsters against contact and airborne transmission of Omicron EG.5.1, demonstrating the functional relevance of durable imprinted antibodies. Together, these findings define the remarkable longevity and molecular basis of antibody imprinting and provide insights for pan-sarbecovirus vaccine design.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"39 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148899075","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}
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