Immunity最新文献_第2页

Retinoic acid and TGF-β orchestrate organ-specific programs of tissue residency 维甲酸和 TGF-β 协调器官特异性组织驻留程序

IF 32.4 1区医学

Immunity Pub Date : 2024-10-14 DOI: 10.1016/j.immuni.2024.09.015

Andreas Obers, Tobias Poch, Grace Rodrigues, Susan N. Christo, Luke C. Gandolfo, Raissa Fonseca, Ali Zaid, Joey En Yu Kuai, Hongjin Lai, Pirooz Zareie, Marina H. Yakou, Lachlan Dryburgh, Thomas N. Burn, James Dosser, Frank A. Buquicchio, Caleb A. Lareau, Calum Walsh, Louise Judd, Maria Rafailia Theodorou, Katharina Gutbrod, Laura K. Mackay

{"title":"Retinoic acid and TGF-β orchestrate organ-specific programs of tissue residency","authors":"Andreas Obers, Tobias Poch, Grace Rodrigues, Susan N. Christo, Luke C. Gandolfo, Raissa Fonseca, Ali Zaid, Joey En Yu Kuai, Hongjin Lai, Pirooz Zareie, Marina H. Yakou, Lachlan Dryburgh, Thomas N. Burn, James Dosser, Frank A. Buquicchio, Caleb A. Lareau, Calum Walsh, Louise Judd, Maria Rafailia Theodorou, Katharina Gutbrod, Laura K. Mackay","doi":"10.1016/j.immuni.2024.09.015","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.09.015","url":null,"abstract":"Tissue-resident memory T (TRM) cells are integral to tissue immunity, persisting in diverse anatomical sites where they adhere to a common transcriptional framework. How these cells integrate distinct local cues to adopt the common TRM cell fate remains poorly understood. Here, we show that whereas skin TRM cells strictly require transforming growth factor β (TGF-β) for tissue residency, those in other locations utilize the metabolite retinoic acid (RA) to drive an alternative differentiation pathway, directing a TGF-β-independent tissue residency program in the liver and synergizing with TGF-β to drive TRM cells in the small intestine. We found that RA was required for the long-term maintenance of intestinal TRM populations, in part by impeding their retrograde migration. Moreover, enhanced RA signaling modulated TRM cell phenotype and function, a phenomenon mirrored in mice with increased microbial diversity. Together, our findings reveal RA as a fundamental component of the host-environment interaction that directs immunosurveillance in tissues.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":null,"pages":null},"PeriodicalIF":32.4,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142431863","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

CRISPR screens unveil nutrient-dependent lysosomal and mitochondrial nodes impacting intestinal tissue-resident memory CD8+ T cell formation CRISPR 筛选揭示了影响肠组织驻留记忆 CD8+ T 细胞形成的营养依赖性溶酶体和线粒体节点

IF 32.4 1区医学

Immunity Pub Date : 2024-10-14 DOI: 10.1016/j.immuni.2024.09.013

Jana L. Raynor, Nicholas Collins, Hao Shi, Cliff Guy, Jordy Saravia, Seon Ah Lim, Nicole M. Chapman, Peipei Zhou, Yan Wang, Yu Sun, Isabel Risch, Haoran Hu, Anil KC, Renqiang Sun, Sharad Shrestha, Hongling Huang, Jon P. Connelly, Shondra M. Pruett-Miller, Miguel Reina-Campos, Ananda W. Goldrath, Hongbo Chi

{"title":"CRISPR screens unveil nutrient-dependent lysosomal and mitochondrial nodes impacting intestinal tissue-resident memory CD8+ T cell formation","authors":"Jana L. Raynor, Nicholas Collins, Hao Shi, Cliff Guy, Jordy Saravia, Seon Ah Lim, Nicole M. Chapman, Peipei Zhou, Yan Wang, Yu Sun, Isabel Risch, Haoran Hu, Anil KC, Renqiang Sun, Sharad Shrestha, Hongling Huang, Jon P. Connelly, Shondra M. Pruett-Miller, Miguel Reina-Campos, Ananda W. Goldrath, Hongbo Chi","doi":"10.1016/j.immuni.2024.09.013","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.09.013","url":null,"abstract":"Nutrient availability and organelle biology direct tissue homeostasis and cell fate, but how these processes orchestrate tissue immunity remains poorly defined. Here, using in vivo CRISPR-Cas9 screens, we uncovered organelle signaling and metabolic processes shaping CD8+ tissue-resident memory T (TRM) cell development. TRM cells depended on mitochondrial translation and respiration. Conversely, three nutrient-dependent lysosomal signaling nodes—Flcn, Ragulator, and Rag GTPases—inhibited intestinal TRM cell formation. Depleting these molecules or amino acids activated the transcription factor Tfeb, thereby linking nutrient stress to TRM programming. Further, Flcn deficiency promoted protective TRM cell responses in the small intestine. Mechanistically, the Flcn-Tfeb axis restrained retinoic acid-induced CCR9 expression for migration and transforming growth factor β (TGF-β)-mediated programming for lineage differentiation. Genetic interaction screening revealed that the mitochondrial protein Mrpl52 enabled early TRM cell formation, while Acss1 controlled TRM cell development under Flcn deficiency-associated lysosomal dysregulation. Thus, the interplay between nutrients, organelle signaling, and metabolic adaptation dictates tissue immunity.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":null,"pages":null},"PeriodicalIF":32.4,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142431864","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

Autoimmune CD4+ T cells fine-tune TCF1 expression to maintain function and survive persistent antigen exposure during diabetes 自身免疫性 CD4+ T 细胞对 TCF1 的表达进行微调，以维持功能并在糖尿病期间持续接触抗原后存活下来

IF 32.4 1区医学

Immunity Pub Date : 2024-10-12 DOI: 10.1016/j.immuni.2024.09.016

Nouf Aljobaily, Denise Allard, Bryant Perkins, Arielle Raugh, Tessa Galland, Yi Jing, W. Zac Stephens, Matthew L. Bettini, J. Scott Hale, Maria Bettini

{"title":"Autoimmune CD4+ T cells fine-tune TCF1 expression to maintain function and survive persistent antigen exposure during diabetes","authors":"Nouf Aljobaily, Denise Allard, Bryant Perkins, Arielle Raugh, Tessa Galland, Yi Jing, W. Zac Stephens, Matthew L. Bettini, J. Scott Hale, Maria Bettini","doi":"10.1016/j.immuni.2024.09.016","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.09.016","url":null,"abstract":"Self-reactive T cells experience chronic antigen exposure but do not exhibit signs of exhaustion. Here, we investigated the mechanisms for sustained, functioning autoimmune CD4+ T cells despite chronic stimulation. Examination of T cell priming showed that CD4+ T cells activated in the absence of infectious signals retained TCF1 expression. At later time points and during blockade of new T cell recruitment, most islet-infiltrating autoimmune CD4+ T cells were TCF1+, although expression was reduced on a per T cell basis. The Tcf7 locus was epigenetically modified in circulating autoimmune CD4+ T cells, suggesting a pre-programmed de novo methylation of the locus in early stages of autoimmune CD4+ T cell differentiation. This mirrored the epigenetic profile of recently recruited CD4+CD62L+ T cells in the pancreas. Collectively, these data reveal a unique environment during autoimmune CD4+ T cell priming that allows T cells to fine-tune TCF1 expression and maintain long-term survival and function.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":null,"pages":null},"PeriodicalIF":32.4,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142415602","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

Microglia and monocyte-derived macrophages drive progression of pediatric high-grade gliomas and are transcriptionally shaped by histone mutations 小胶质细胞和单核细胞衍生巨噬细胞推动小儿高级别胶质瘤的发展，并通过组蛋白突变形成转录

IF 32.4 1区医学

Immunity Pub Date : 2024-10-11 DOI: 10.1016/j.immuni.2024.09.007

James L. Ross, Montserrat Puigdelloses-Vallcorba, Gonzalo Piñero, Nishant Soni, Wes Thomason, John DeSisto, Angelo Angione, Nadejda M. Tsankova, Maria G. Castro, Matthew Schniederjan, Nitin R. Wadhwani, G. Praveen Raju, Peter Morgenstern, Oren J. Becher, Adam L. Green, Alexander M. Tsankov, Dolores Hambardzumyan

{"title":"Microglia and monocyte-derived macrophages drive progression of pediatric high-grade gliomas and are transcriptionally shaped by histone mutations","authors":"James L. Ross, Montserrat Puigdelloses-Vallcorba, Gonzalo Piñero, Nishant Soni, Wes Thomason, John DeSisto, Angelo Angione, Nadejda M. Tsankova, Maria G. Castro, Matthew Schniederjan, Nitin R. Wadhwani, G. Praveen Raju, Peter Morgenstern, Oren J. Becher, Adam L. Green, Alexander M. Tsankov, Dolores Hambardzumyan","doi":"10.1016/j.immuni.2024.09.007","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.09.007","url":null,"abstract":"Pediatric high-grade gliomas (pHGGs), including hemispheric pHGGs and diffuse midline gliomas (DMGs), harbor mutually exclusive tumor location-specific histone mutations. Using immunocompetent de novo mouse models of pHGGs, we demonstrated that myeloid cells were the predominant infiltrating non-neoplastic cell population. Single-cell RNA sequencing (scRNA-seq), flow cytometry, and immunohistochemistry illustrated the presence of heterogeneous myeloid cell populations shaped by histone mutations and tumor location. Disease-associated myeloid (DAM) cell phenotypes demonstrating immune permissive characteristics were identified in murine and human pHGG samples. H3.3K27M DMGs, the most aggressive DMG, demonstrated enrichment of DAMs. Genetic ablation of chemokines Ccl8 and Ccl12 resulted in a reduction of DAMs and an increase in lymphocyte infiltration, leading to increased survival of tumor-bearing mice. Pharmacologic inhibition of chemokine receptors CCR1 and CCR5 resulted in extended survival and decreased myeloid cell infiltration. This work establishes the tumor-promoting role of myeloid cells in DMG and the potential therapeutic opportunities for targeting them.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":null,"pages":null},"PeriodicalIF":32.4,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142405141","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

TIL the end: Tracking T cell clonotype dynamics during adoptive cell therapy TIL 终结：追踪采用细胞疗法期间 T 细胞克隆型的动态变化

IF 32.4 1区医学

Immunity Pub Date : 2024-10-08 DOI: 10.1016/j.immuni.2024.09.012

Anthony C. Buzzai, Thomas Tüting

引用次数: 0

Antigen-presenting cells as specialized drivers of intestinal T cell functions 抗原递呈细胞是肠道 T 细胞功能的专门驱动力

IF 32.4 1区医学

Immunity Pub Date : 2024-10-08 DOI: 10.1016/j.immuni.2024.09.011

Ranit Kedmi, Dan R. Littman

引用次数: 0

Oligodendrocytes go with the flow: Meningeal lymphatics promote myelin integrity 少突胶质细胞随波逐流脑膜淋巴管促进髓鞘完整性

IF 32.4 1区医学

Immunity Pub Date : 2024-10-08 DOI: 10.1016/j.immuni.2024.09.006

Eric D. Garcia, Jonah R. Chan

引用次数: 0

An autoreactive T cell’s perception of a land of plenty 自反应 T 细胞对富饶之地的感知

IF 32.4 1区医学

Immunity Pub Date : 2024-10-08 DOI: 10.1016/j.immuni.2024.09.005

Thomas Korn

引用次数: 0

An explainable language model for antibody specificity prediction using curated influenza hemagglutinin antibodies. 使用经整理的流感血凝素抗体预测抗体特异性的可解释语言模型。

IF 25.5 1区医学

Immunity Pub Date : 2024-10-08 Epub Date: 2024-08-19 DOI: 10.1016/j.immuni.2024.07.022

Yiquan Wang, Huibin Lv, Qi Wen Teo, Ruipeng Lei, Akshita B Gopal, Wenhao O Ouyang, Yuen-Hei Yeung, Timothy J C Tan, Danbi Choi, Ivana R Shen, Xin Chen, Claire S Graham, Nicholas C Wu

{"title":"An explainable language model for antibody specificity prediction using curated influenza hemagglutinin antibodies.","authors":"Yiquan Wang, Huibin Lv, Qi Wen Teo, Ruipeng Lei, Akshita B Gopal, Wenhao O Ouyang, Yuen-Hei Yeung, Timothy J C Tan, Danbi Choi, Ivana R Shen, Xin Chen, Claire S Graham, Nicholas C Wu","doi":"10.1016/j.immuni.2024.07.022","DOIUrl":"10.1016/j.immuni.2024.07.022","url":null,"abstract":"Despite decades of antibody research, it remains challenging to predict the specificity of an antibody solely based on its sequence. Two major obstacles are the lack of appropriate models and the inaccessibility of datasets for model training. In this study, we curated >5,000 influenza hemagglutinin (HA) antibodies by mining research publications and patents, which revealed many distinct sequence features between antibodies to HA head and stem domains. We then leveraged this dataset to develop a lightweight memory B cell language model (mBLM) for sequence-based antibody specificity prediction. Model explainability analysis showed that mBLM could identify key sequence features of HA stem antibodies. Additionally, by applying mBLM to HA antibodies with unknown epitopes, we discovered and experimentally validated many HA stem antibodies. Overall, this study not only advances our molecular understanding of the antibody response to the influenza virus but also provides a valuable resource for applying deep learning to antibody research.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":null,"pages":null},"PeriodicalIF":25.5,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464180/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142008755","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}

引用次数: 0

LAGging behind no more: PD-1 has a new immunotherapy partner 不再落后PD-1 有了新的免疫疗法伙伴

IF 32.4 1区医学

Immunity Pub Date : 2024-10-08 DOI: 10.1016/j.immuni.2024.09.010

Andrew J. Gunderson

引用次数: 0