Immunity最新文献

Deep profiling deconstructs features associated with memory CD8+ T cell tissue residence

IF 32.4 1区医学

Immunity Pub Date : 2024-12-20 DOI: 10.1016/j.immuni.2024.11.007

Milcah C. Scott, Zoë Steier, Mark J. Pierson, J. Michael Stolley, Stephen D. O’Flanagan, Andrew G. Soerens, Sathi P. Wijeyesinghe, Lalit K. Beura, Gayathri Dileepan, Brandon J. Burbach, Marco Künzli, Clare F. Quarnstrom, Olivia C. Ghirardelli Smith, Eyob Weyu, Sara E. Hamilton, Vaiva Vezys, Alex K. Shalek, David Masopust

{"title":"Deep profiling deconstructs features associated with memory CD8+ T cell tissue residence","authors":"Milcah C. Scott, Zoë Steier, Mark J. Pierson, J. Michael Stolley, Stephen D. O’Flanagan, Andrew G. Soerens, Sathi P. Wijeyesinghe, Lalit K. Beura, Gayathri Dileepan, Brandon J. Burbach, Marco Künzli, Clare F. Quarnstrom, Olivia C. Ghirardelli Smith, Eyob Weyu, Sara E. Hamilton, Vaiva Vezys, Alex K. Shalek, David Masopust","doi":"10.1016/j.immuni.2024.11.007","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.11.007","url":null,"abstract":"Tissue-resident memory CD8+ T (Trm) cells control infections and cancer and are defined by their lack of recirculation. Because migration is difficult to assess, residence is usually inferred by putative residence-defining phenotypic and gene signature proxies. We assessed the validity and universality of residence proxies by integrating mouse parabiosis, multi-organ sampling, intravascular staining, acute and chronic infection models, dirty mice, and single-cell multi-omics. We report that memory T cells integrate a constellation of inputs—location, stimulation history, antigen persistence, and environment—resulting in myriad differentiation states. Thus, current Trm-defining methodologies have implicit limitations, and a universal residence-specific signature may not exist. However, we define genes and phenotypes that more robustly correlate with tissue residence across the broad range of conditions that we tested. This study reveals broad adaptability of T cells to diverse stimulatory and environmental inputs and provides practical recommendations for evaluating Trm cells.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"22 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142857805","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 carbonyl nucleobase adduct M3Ade is a potent antigen for adaptive polyclonal MR1-restricted T cells

IF 32.4 1区医学

Immunity Pub Date : 2024-12-18 DOI: 10.1016/j.immuni.2024.11.019

Andrew Chancellor, Daniel Constantin, , Qinmei Yang, Vladimir Nosi, José Pedro Loureiro, Rodrigo Colombo, Roman P. Jakob, Daniel Joss, Michael Pfeffer, Giulia De Simone, Aurelia Morabito, Verena Schaefer, Alessandro Vacchini, Laura Brunelli, Daniela Montagna, Markus Heim, Alfred Zippelius, Enrico Davoli, Daniel Häussinger, Gennaro De Libero

{"title":"The carbonyl nucleobase adduct M3Ade is a potent antigen for adaptive polyclonal MR1-restricted T cells","authors":"Andrew Chancellor, Daniel Constantin, , Qinmei Yang, Vladimir Nosi, José Pedro Loureiro, Rodrigo Colombo, Roman P. Jakob, Daniel Joss, Michael Pfeffer, Giulia De Simone, Aurelia Morabito, Verena Schaefer, Alessandro Vacchini, Laura Brunelli, Daniela Montagna, Markus Heim, Alfred Zippelius, Enrico Davoli, Daniel Häussinger, Gennaro De Libero","doi":"10.1016/j.immuni.2024.11.019","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.11.019","url":null,"abstract":"The major histocompatibility complex (MHC) class I-related molecule MHC-class-I-related protein 1 (MR1) presents metabolites to distinct MR1-restricted T cell subsets, including mucosal-associated invariant T (MAIT) and MR1T cells. However, self-reactive MR1T cells and the nature of recognized antigens remain underexplored. Here, we report a cell endogenous carbonyl adduct of adenine (8-(9H-purin-6-yl)-2-oxa-8-azabicyclo[3.3.1]nona-3,6-diene-4,6-dicarbaldehyde [M3Ade]) sequestered in the A′ pocket of MR1. M3Ade induced in vitro MR1-mediated stimulation of MR1T cell clones that bound MR1-M3Ade tetramers. MR1-M3Ade tetramers identified heterogeneous MR1-reactive T cells ex vivo in healthy donors, individuals with acute myeloid leukemia, and tumor-infiltrating lymphocytes from non-small cell lung adenocarcinoma and hepatocarcinoma. These cells displayed phenotypic, transcriptional, and functional diversity at distinct differentiation stages, indicating their adaptive nature. They were also polyclonal, with some preferential T cell receptor (TCRαβ) pair usage. Thus, M3Ade is an MR1-presented self-metabolite that enables stimulation and tracking of human-MR1T cells from blood and tissue, aiding our understanding of their roles in health and disease.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"78 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841517","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 cGAS-STING pathway activates transcription factor TFEB to stimulate lysosome biogenesis and pathogen clearance cGAS-STING 通路激活转录因子 TFEB，刺激溶酶体生物生成和病原体清除

IF 32.4 1区医学

Immunity Pub Date : 2024-12-16 DOI: 10.1016/j.immuni.2024.11.017

Yinfeng Xu, Qian Wang, Jun Wang, Chuying Qian, Yusha Wang, Sheng Lu, Lijiang Song, Zhengfu He, Wei Liu, Wei Wan

{"title":"The cGAS-STING pathway activates transcription factor TFEB to stimulate lysosome biogenesis and pathogen clearance","authors":"Yinfeng Xu, Qian Wang, Jun Wang, Chuying Qian, Yusha Wang, Sheng Lu, Lijiang Song, Zhengfu He, Wei Liu, Wei Wan","doi":"10.1016/j.immuni.2024.11.017","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.11.017","url":null,"abstract":"Induction of autophagy is an ancient function of the cyclic GMP-AMP (cGAMP) synthase (cGAS)-stimulator of interferon genes (STING) pathway through which autophagic cargoes are delivered to lysosomes for degradation. However, whether lysosome function is also modulated by the cGAS-STING pathway remains unknown. Here, we discovered that the cGAS-STING pathway upregulated lysosomal activity by stimulating lysosome biogenesis independently of the downstream protein kinase TANK-binding kinase 1 (TBK1). STING activation enhanced lysosome biogenesis through inducing the nuclear translocation of transcription factor EB (TFEB) as well as its paralogs transcription factor E3 (TFE3) and microphthalmia-associated transcription factor (MITF). STING-induced lipidation of GABA type A receptor-associated protein (GABARAP), an autophagy-related protein, on STING vesicles was responsible for TFEB activation. Membrane-bound GABARAP sequestered the GTPase-activating protein folliculin (FLCN) and FLCN-interacting protein (FNIP) complex to block its function toward the Rag GTPases Ras-related GTP-binding C and D (RagC and RagD), abolishing mechanistic target of rapamycin (mTOR) complex 1 (mTORC1)-dependent phosphorylation and inactivation of TFEB. Functionally, STING-induced lysosome biogenesis within cells facilitated the clearance of cytoplasmic DNA and invading pathogens. Thus, our findings reveal that induction of lysosome biogenesis is another important function of the cGAS-STING pathway.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"22 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142825551","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

Hidradenitis suppurativa: TLSs take the center stage

IF 32.4 1区医学

Immunity Pub Date : 2024-12-10 DOI: 10.1016/j.immuni.2024.11.011

Cody Elkins, Chaoran Li

引用次数: 0

Skin immune-mesenchymal interplay within tertiarylymphoid structures promotes autoimmunepathogenesis in hidradenitis suppurativa 三级淋巴结构中的皮肤免疫-间质相互作用促进了化脓性扁桃体炎的自身免疫发病机制

IF 32.4 1区医学

Immunity Pub Date : 2024-12-10 DOI: 10.1016/j.immuni.2024.11.010

Wei-Wen Yu, Joy N.P. Barrett, Jie Tong, Meng-Ju Lin, Meaghan Marohn, Joseph C. Devlin, Alberto Herrera, Juliana Remark, Jamie Levine, Pei-Kang Liu, Victoria Fang, Abigail M. Zellmer, Derek A. Oldridge, E. John Wherry, Jia-Ren Lin, Jia-Yun Chen, Peter Sorger, Sandro Santagata, James G. Krueger, Kelly V. Ruggles, Catherine P. Lu

{"title":"Skin immune-mesenchymal interplay within tertiarylymphoid structures promotes autoimmunepathogenesis in hidradenitis suppurativa","authors":"Wei-Wen Yu, Joy N.P. Barrett, Jie Tong, Meng-Ju Lin, Meaghan Marohn, Joseph C. Devlin, Alberto Herrera, Juliana Remark, Jamie Levine, Pei-Kang Liu, Victoria Fang, Abigail M. Zellmer, Derek A. Oldridge, E. John Wherry, Jia-Ren Lin, Jia-Yun Chen, Peter Sorger, Sandro Santagata, James G. Krueger, Kelly V. Ruggles, Catherine P. Lu","doi":"10.1016/j.immuni.2024.11.010","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.11.010","url":null,"abstract":"Hidradenitis suppurativa (HS) is a chronic, debilitating inflammatory skin disease characterized by keratinized epithelial tunnels that grow deeply into the dermis. Here, we examined the immune microenvironment within human HS lesions. Multi-omics profiling and multiplexed imaging identified tertiary lymphoid structures (TLSs) near HS tunnels. These TLSs were enriched with proliferative T cells, including follicular helper (Tfh), regulatory (Treg), and pathogenic T cells (IL17A+ and IFNG+), alongside extensive clonal expansion of plasma cells producing antibodies reactive to keratinocytes. HS fibroblasts express CXCL13 or CCL19 in response to immune cytokines. Using a microfluidic system to mimic TLS on a chip, we found that HS fibroblasts critically orchestrated lymphocyte aggregation via tumor necrosis factor alpha (TNF-α)-CXCL13 and TNF-α-CCL19 feedback loops with B and T cells, respectively; early TNF-α blockade suppressed aggregate initiation. Our findings provide insights into TLS formation in the skin, suggest therapeutic avenues for HS, and reveal mechanisms that may apply to other autoimmune settings, including Crohn’s disease.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"37 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142797596","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

T-switch-ing TCR specificity

IF 32.4 1区医学

Immunity Pub Date : 2024-12-10 DOI: 10.1016/j.immuni.2024.11.014

Andrew Y. Hu, Cristina Puig-Saus

引用次数: 0

DC-T cell power couples in rheumatoid arthritis joints

IF 32.4 1区医学

Immunity Pub Date : 2024-12-10 DOI: 10.1016/j.immuni.2024.11.012

Kazuhiko Higashioka, Deepak A. Rao

引用次数: 0

Beyond classical immunity: Mast cells as signal converters between tissues and neurons