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The endogenous antigen-specific CD8+ T cell repertoire is composed of unbiased and biased clonotypes with differential fate commitments
IF 32.4 1区 医学
Immunity Pub Date : 2025-02-27 DOI: 10.1016/j.immuni.2025.02.001
Leena Abdullah, Francesco E. Emiliani, Chinmay M. Vaidya, Hannah Stuart, Shawn C. Musial, Fred W. Kolling, Joshua J. Obar, Pamela C. Rosato, Margaret E. Ackerman, Li Song, Aaron McKenna, Yina H. Huang
{"title":"The endogenous antigen-specific CD8+ T cell repertoire is composed of unbiased and biased clonotypes with differential fate commitments","authors":"Leena Abdullah, Francesco E. Emiliani, Chinmay M. Vaidya, Hannah Stuart, Shawn C. Musial, Fred W. Kolling, Joshua J. Obar, Pamela C. Rosato, Margaret E. Ackerman, Li Song, Aaron McKenna, Yina H. Huang","doi":"10.1016/j.immuni.2025.02.001","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.02.001","url":null,"abstract":"Generating balanced populations of CD8<sup>+</sup> effector and memory T cells is necessary for immediate and durable immunity to infections and cancer. Yet, a definitive understanding of how a diverse CD8<sup>+</sup> T cell repertoire differentiates remains unclear. We identified several hundred T cell receptor (TCR) clonotypes that constitute the polyclonal response against a single antigen and found that a majority of TCR clonotypes were highly biased toward memory or effector fates. TCR-intrinsic biases were not stochastic and were dominant over environmental cues. Differential gene expression analysis of memory- or effector-biased TCR clonotypes showed bifurcation of differential fates at the early effector stage. Additionally, phylogenetic analysis revealed that memory-biased clonotypes retain their fate preferences in subclonal populations but effector-biased subclones can switch to a memory fate. Our study highlights that the polyclonal CD8<sup>+</sup> T cell response is a composite of unbiased and biased clonotypes with varying capacity to incorporate environmental cues in their cell fate decisions.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"28 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506909","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
A bladder-blood immune barrier constituted by suburothelial perivascular macrophages restrains uropathogen dissemination
IF 32.4 1区 医学
Immunity Pub Date : 2025-02-26 DOI: 10.1016/j.immuni.2025.02.002
Lu Li, Qiancheng Jiao, Qianqian Yang, Haisen Lu, Xia Zhou, Qing Zhang, Futing Zhang, Hai Li, Zhigang Tian, Zhutian Zeng
{"title":"A bladder-blood immune barrier constituted by suburothelial perivascular macrophages restrains uropathogen dissemination","authors":"Lu Li, Qiancheng Jiao, Qianqian Yang, Haisen Lu, Xia Zhou, Qing Zhang, Futing Zhang, Hai Li, Zhigang Tian, Zhutian Zeng","doi":"10.1016/j.immuni.2025.02.002","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.02.002","url":null,"abstract":"Urinary tract infections (UTIs) predominantly occur in the bladder and can potentially progress into life-threatening sepsis if uropathogens spread unconstrainedly into the bloodstream. Here, we identified a subset of suburothelial perivascular macrophages (suPVMs) in the bladder that exerted a pivotal barrier function to prevent systemic bacterial dissemination during acute cystitis. During the initial phase of uropathogenic <em>Escherichia coli</em> (UPEC) infection, suPVMs actively captured UPEC invading the laminal propria and maintained the integrity of inflamed vessels. They subsequently underwent METosis to expel macrophage extracellular DNA traps (METs) into the urothelium to sequester bacteria within this avascular compartment. Matrix metallopeptidase-13 was released along with METs to promote neutrophil transuroepithelial migration. Replenished suPVMs from monocytes following a prior infection were functionally competent to confer protection against recurrent UTIs. Our study thus uncovers a bladder-blood immune barrier in restraining uropathogen dissemination, which could have implications for the prevention and treatment of urosepsis.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"12 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143495776","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
OAS cross-activates RNase L intercellularly through cell-to-cell transfer of 2-5A to spread innate immunity
IF 32.4 1区 医学
Immunity Pub Date : 2025-02-25 DOI: 10.1016/j.immuni.2025.01.016
Wanwan Huai, Kun Yang, Cong Xing, Kun Song, Heng Lyu, Noelle S. Williams, Jianjun Wu, Nan Yan
{"title":"OAS cross-activates RNase L intercellularly through cell-to-cell transfer of 2-5A to spread innate immunity","authors":"Wanwan Huai, Kun Yang, Cong Xing, Kun Song, Heng Lyu, Noelle S. Williams, Jianjun Wu, Nan Yan","doi":"10.1016/j.immuni.2025.01.016","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.01.016","url":null,"abstract":"The 2′,5′-oligoadenylate synthetase (OAS)-RNase L pathway is a classical antiviral innate immune pathway. Upon sensing dsRNA, OAS produces 2′,5′-oligoadenylate (2-5A) as a second messenger to activate RNase L. Whether 2-5A can be transported to extend the reach of innate immune signaling has not been established. Here, we showed that 2-5A was transferred from cell to cell through connexin (CX43/CX45) gap junctions. 2-5A was also transferred through importers and exporters, allowing OAS to remotely activate RNase L and protect neighboring cells from viral infection. We identified ABCC10 as a 2-5A exporter. Loss of ABCC10 had no effect on 2-5A production but reduced 2-5A export and protection of neighboring cells. Furthermore, OAS<sup>hi</sup> tumors such as MC38 naturally produced 2-5A <em>in vivo</em>, which was secreted via ABCC10 to activate host—not tumor—RNase L-mediated antitumor response. Therefore, 2-5A is an immunotransmitter that mediates short-range communication between cells in infection and cancer.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"16 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143486526","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
The kinase RIPK3 promotes neuronal survival by suppressing excitatory neurotransmission during central nervous system viral infection
IF 32.4 1区 医学
Immunity Pub Date : 2025-02-24 DOI: 10.1016/j.immuni.2025.01.017
Irving Estevez, Benjamin D. Buckley, Marissa Lindman, Nicholas Panzera, Tsui-Wen Chou, Micheal McCourt, Brandon J. Vaglio, Colm Atkins, Bonnie L. Firestein, Brian P. Daniels
{"title":"The kinase RIPK3 promotes neuronal survival by suppressing excitatory neurotransmission during central nervous system viral infection","authors":"Irving Estevez, Benjamin D. Buckley, Marissa Lindman, Nicholas Panzera, Tsui-Wen Chou, Micheal McCourt, Brandon J. Vaglio, Colm Atkins, Bonnie L. Firestein, Brian P. Daniels","doi":"10.1016/j.immuni.2025.01.017","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.01.017","url":null,"abstract":"While recent work has identified roles for immune mediators in regulating neural activity, how innate immune signaling within neurons influences neurotransmission remains poorly understood. Emerging evidence suggests that the modulation of neurotransmission may serve important roles in host protection during infection of the central nervous system. Here, we showed that receptor-interacting protein kinase-3 (RIPK3) preserved neuronal survival during flavivirus infection through the suppression of excitatory neurotransmission. These effects occurred independently of the traditional functions of RIPK3 in promoting necroptosis and inflammatory transcription. Instead, RIPK3 promoted phosphorylation of the neuronal regulatory kinase calcium/calmodulin-dependent protein kinase II (CaMKII), which in turn activated the transcription factor cyclic AMP response element-binding protein (CREB) to drive a neuroprotective transcriptional program and suppress deleterious glutamatergic signaling. These findings identify an unexpected function for a canonical cell death protein in promoting neuronal survival during viral infection through the modulation of neuronal activity, highlighting mechanisms of neuroimmune crosstalk.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"30 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477750","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
Bacterial translocation promotes trained immunity
IF 32.4 1区 医学
Immunity Pub Date : 2025-02-11 DOI: 10.1016/j.immuni.2025.01.011
Maria Francesca Viola, Elvira Mass
{"title":"Bacterial translocation promotes trained immunity","authors":"Maria Francesca Viola, Elvira Mass","doi":"10.1016/j.immuni.2025.01.011","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.01.011","url":null,"abstract":"Can bacteria that breach mucosal barriers drive long-lasting changes in immunity? In this issue of <em>Immunity</em>, Robles-Vera et al. describe how, in the context of colitis, bacteria breaching the intestinal barrier reprogram precursors in the bone marrow via Mincle-dependent signaling.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"86 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143385244","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
Nerve-racking worms
IF 32.4 1区 医学
Immunity Pub Date : 2025-02-11 DOI: 10.1016/j.immuni.2025.01.014
Yisi Lu, Ruaidhrí Jackson
{"title":"Nerve-racking worms","authors":"Yisi Lu, Ruaidhrí Jackson","doi":"10.1016/j.immuni.2025.01.014","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.01.014","url":null,"abstract":"The enteric nervous system is a key regulator of inflammation, crosstalking directly with the immune system at the mucosal surfaces of the gastrointestinal tract. In this issue of <em>Immunity</em>, Wang and colleagues demonstrate that intrinsic enteric neurons (iENs) sense interleukin (IL)-13 to restrain group 2 innate lymphoid cell (ILC2) activity during helminth infection, uncovering a novel neuro-immune-regulatory circuit.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"13 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143384964","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
Early-age efferocytosis directs macrophage arachidonic acid metabolism for tissue regeneration
IF 32.4 1区 医学
Immunity Pub Date : 2025-02-11 DOI: 10.1016/j.immuni.2024.11.018
Connor Lantz, Amanda Becker, Matthew DeBerge, Mallory Filipp, Kristofor Glinton, Aparnaa Ananthakrishnan, Jessica Urbanczyk, Madeline Cetlin, Afnan Alzamroon, Ahmed Abdel-Latif, Matthew Spite, Zhi-Dong Ge, Edward B. Thorp
{"title":"Early-age efferocytosis directs macrophage arachidonic acid metabolism for tissue regeneration","authors":"Connor Lantz, Amanda Becker, Matthew DeBerge, Mallory Filipp, Kristofor Glinton, Aparnaa Ananthakrishnan, Jessica Urbanczyk, Madeline Cetlin, Afnan Alzamroon, Ahmed Abdel-Latif, Matthew Spite, Zhi-Dong Ge, Edward B. Thorp","doi":"10.1016/j.immuni.2024.11.018","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.11.018","url":null,"abstract":"In response to organ injury in adults, macrophages often promote scarring, yet during early life, they are required for tissue regeneration. To elucidate the mechanisms underlying age-associated regeneration, we compared the macrophage injury response in newborn versus adult hearts. Single-cell analysis revealed an accumulation of tissue-resident macrophages in neonates that were selectively polarized for apoptotic cell recognition and uptake (efferocytosis). Ablation of the apoptotic cell recognition receptor <em>Mertk</em> in newborns prevented cardiac regeneration. These findings could be attributed to reprogramming of macrophage gene expression that was required for biosynthesis of the eicosanoid thromboxane A<sub>2</sub>, which unexpectedly activated parenchymal cell proliferation. Markers of thromboxane A<sub>2</sub> production were suppressed in adult macrophages after efferocytosis. Moreover, macrophage-neighboring neonatal cardiomyocytes expressed the thromboxane A<sub>2</sub> receptor, whose activation induced a metabolic shift that supported cellular proliferation. Our data reveal a fundamental age-defined macrophage response in which lipid mitogens produced during efferocytosis support receptor-mediated tissue regeneration.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"16 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143384966","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
Cutting to the chase: Pruning alloreactive T cells
IF 32.4 1区 医学
Immunity Pub Date : 2025-02-11 DOI: 10.1016/j.immuni.2025.01.005
Anita S. Chong, Marlena Habal
{"title":"Cutting to the chase: Pruning alloreactive T cells","authors":"Anita S. Chong, Marlena Habal","doi":"10.1016/j.immuni.2025.01.005","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.01.005","url":null,"abstract":"Indirect CD4<sup>+</sup> T cell allorecognition of donor peptides presented by host MHC class II antigens contributes to transplant rejection in part by eliciting donor-specific antibodies (DSAs). In this issue of <em>Immunity</em>, Zhanzak et al. revisit the role of indirectly alloreactive CD4<sup>+</sup> T cells in transplantation and demonstrate that immunodominant epitopes stimulate a narrow repertoire of T cells that can be pruned to prevent DSA formation.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"41 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143384963","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
Everything everywhere all at once: Unraveling the waves of aging
IF 32.4 1区 医学
Immunity Pub Date : 2025-02-11 DOI: 10.1016/j.immuni.2025.01.015
Jose Ignacio Escrig-Larena, María Mittelbrunn
{"title":"Everything everywhere all at once: Unraveling the waves of aging","authors":"Jose Ignacio Escrig-Larena, María Mittelbrunn","doi":"10.1016/j.immuni.2025.01.015","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.01.015","url":null,"abstract":"In a recent work reported in <em>Science,</em> Zhang et al. untangle dynamic changes arising across aging in multiple cell populations within thirteen organs using single-cell transcriptomics and identify four distinct dynamic waves in which immune cells are the most affected populations.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"3 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143384965","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
Next generation lysosome: Brought to you by cGAS-STING
IF 32.4 1区 医学
Immunity Pub Date : 2025-02-11 DOI: 10.1016/j.immuni.2025.01.012
Lei Wang, Wen Zhou
{"title":"Next generation lysosome: Brought to you by cGAS-STING","authors":"Lei Wang, Wen Zhou","doi":"10.1016/j.immuni.2025.01.012","DOIUrl":"https://doi.org/10.1016/j.immuni.2025.01.012","url":null,"abstract":"Renowned for driving interferon responses, the cGAS-STING pathway reveals a surprising role: lysosomal biogenesis. In this issue of <em>Immunity</em>, Xu et al. uncover how STING activates the transcription factor TFEB, linking innate immune sensing to enhanced pathogen clearance through lysosomal activity.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"31 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143385243","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
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