Immunity最新文献_第7页

Copy and paste: Humanizing IgH 155 kb at a time. 复制和粘贴：每次人性化155kb。

IF 30.6 1区医学

Immunity Pub Date : 2026-08-11 DOI: 10.1016/j.immuni.2026.07.015

Tianli Xiao, Richard A Flavell

引用次数: 0

Purine and pyrimidine-based bacterial cyclic dinucleotides egress the phagosome and activate the innate immune sensor STING. 嘌呤和嘧啶为基础的细菌环二核苷酸出口吞噬体和激活先天免疫传感器STING。

IF 30.6 1区医学

Immunity Pub Date : 2026-08-11 Epub Date: 2026-07-17 DOI: 10.1016/j.immuni.2026.06.023

Stephanie A Ragland, Katherine E Lindblad, Yao Li, Joon H Choi, Daniel Okin, Joshua Q Mao, Desmond Richmond-Buccola, Daniela R Coronado, Madison R Brown, Scott B Snapper, Philip J Kranzusch, Jonathan C Kagan

{"title":"Purine and pyrimidine-based bacterial cyclic dinucleotides egress the phagosome and activate the innate immune sensor STING.","authors":"Stephanie A Ragland, Katherine E Lindblad, Yao Li, Joon H Choi, Daniel Okin, Joshua Q Mao, Desmond Richmond-Buccola, Daniela R Coronado, Madison R Brown, Scott B Snapper, Philip J Kranzusch, Jonathan C Kagan","doi":"10.1016/j.immuni.2026.06.023","DOIUrl":"10.1016/j.immuni.2026.06.023","url":null,"abstract":"Toll-like receptors (TLRs) are considered general sensors of bacterial encounters. Here, we examined whether other pattern recognition receptors are commonly activated during bacterial infection. TLR-independent interferon (IFN) responses were induced in macrophages in response to diverse bacterial encounters. Of the cytoplasmic receptor families examined, the cyclic dinucleotide (CDN) sensor STING was required for IFN responses to evolutionarily diverse bacteria. Various bacterial CDNs were present in murine tissues; these activated stimulator of interferon genes (STING) after bacteriolysis in phagolysosomes in a manner requiring two CDN transporters. Importantly, bacterial CDNs were increased in colonic biopsies from patients with inflammatory bowel disease. Systemic delivery of dead, CDN-laden bacteria promoted anti-tumor immunity in mice. Detection of diverse CDNs, including pyrimidine-based CDNs, was an evolutionarily conserved feature of STING, with distinct binding modes for purine- and pyrimidine-based CDNs. Thus, a phagocytosis-CDN-STING connection places cytoplasmic sensing as a common outcome of host-bacteria interactions that set the immune tone of a tissue, with implications for host defense.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":" ","pages":"2086-2105.e17"},"PeriodicalIF":30.6,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13379678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148470075","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

Interleukin 23 promotes a pro-inflammatory Th17 cell state by stabilizing RORγt and suppressing glucocorticoid receptor activity. 白细胞介素23通过稳定rr γt和抑制糖皮质激素受体活性来促进促炎Th17细胞状态。

IF 30.6 1区医学

Immunity Pub Date : 2026-08-11 Epub Date: 2026-06-12 DOI: 10.1016/j.immuni.2026.05.016

Dandan Yang, Linglin Huang, Jianfei Yang, Oier Etxezarreta-Arrastoa, Markus A Schramm, Alex V Khodaverdian, Nandini Acharya, Sai Harsha Krovi, Karen Dixon, Hanning Cheng, Katherine L Wei, Junrong Xia, Fan Cheng, Alissa J Nelson, Kathryn Abell, Jian Min Ren, Vicky Yang, Timothy Sikorski, Roland Annan, Stephanie Van Horn, Christopher Traini, Thad Carlson, Rajesh K Krishnan, Matthew P Stokes, Raymond A Sobel, Nir Yosef, Ana C Anderson, Vijay K Kuchroo

{"title":"Interleukin 23 promotes a pro-inflammatory Th17 cell state by stabilizing RORγt and suppressing glucocorticoid receptor activity.","authors":"Dandan Yang, Linglin Huang, Jianfei Yang, Oier Etxezarreta-Arrastoa, Markus A Schramm, Alex V Khodaverdian, Nandini Acharya, Sai Harsha Krovi, Karen Dixon, Hanning Cheng, Katherine L Wei, Junrong Xia, Fan Cheng, Alissa J Nelson, Kathryn Abell, Jian Min Ren, Vicky Yang, Timothy Sikorski, Roland Annan, Stephanie Van Horn, Christopher Traini, Thad Carlson, Rajesh K Krishnan, Matthew P Stokes, Raymond A Sobel, Nir Yosef, Ana C Anderson, Vijay K Kuchroo","doi":"10.1016/j.immuni.2026.05.016","DOIUrl":"10.1016/j.immuni.2026.05.016","url":null,"abstract":"Interleukin 23 receptor (IL-23R) signaling is critical for the generation of pro-inflammatory CD4+ IL-17-producing T helper cells (Th17) that can drive autoimmune tissue inflammation, but the underlying mechanisms are not clear. We integrated phosphoproteomic and transcriptomic data downstream of IL-23R and IL-12 receptor (IL-12R), which share a common subunit, to identify mechanisms engaged specifically by IL-23. We identified chromodomain helicase DNA-binding protein 1 (CHD1), an epigenetic regulator, and the glucocorticoid receptor (GR), a transcription factor (TF), as mediators of IL-23R signaling. IL-23R activation promoted CHD1 interaction with TF STAT3 and co-binding at the TF RORγt locus to enforce a pro-inflammatory Th17 state. Conversely, IL-23R signaling altered phosphorylation of the GR, thereby preventing its activation and nuclear translocation, ultimately impairing GR-driven inhibition of pro-inflammatory Th17 gene programs. Our findings uncover two mechanisms by which IL-23 promotes a pro-inflammatory Th17 cell state, offering potential therapeutic targets for treating Th17-driven autoimmune tissue inflammation and restoring homeostasis.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":" ","pages":"2250-2265.e11"},"PeriodicalIF":30.6,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148239188","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-mediated precise large fragment insertion in zygotes enables rapid generation of humanized immunoglobulin heavy-chain mice. crispr介导的精确大片段插入受精卵能够快速产生人源化免疫球蛋白重链小鼠。

IF 30.6 1区医学

Immunity Pub Date : 2026-08-11 Epub Date: 2026-07-09 DOI: 10.1016/j.immuni.2026.06.008

Usha Nair, Madhav Akauliya, John E Warner, Shivang Parikh, Larance Ronsard, Maria Ssozi, Larissa Rays Wahba, Abigail G Esposito, Brendon Kelley, Caitlin McCarthy, Stephanie R Weldon, Lin Wu, Daniel Lingwood, Facundo D Batista

{"title":"CRISPR-mediated precise large fragment insertion in zygotes enables rapid generation of humanized immunoglobulin heavy-chain mice.","authors":"Usha Nair, Madhav Akauliya, John E Warner, Shivang Parikh, Larance Ronsard, Maria Ssozi, Larissa Rays Wahba, Abigail G Esposito, Brendon Kelley, Caitlin McCarthy, Stephanie R Weldon, Lin Wu, Daniel Lingwood, Facundo D Batista","doi":"10.1016/j.immuni.2026.06.008","DOIUrl":"10.1016/j.immuni.2026.06.008","url":null,"abstract":"Current CRISPR-Cas9 methods are restricted to small genomic edits. We developed a CRISPR-guided approach that enables direct insertion of large genomic sequences into mouse zygotes. We deleted the murine 2.4-Mb immunoglobulin heavy-chain (IgH) variable (VH) locus and then precisely inserted a bacterial artificial chromosome (BAC) containing a 155-kb human VH DNA fragment flanked by 20-kb homology arms. Full-length, single-copy BAC integration occurred without ectopic recombination. Human sequences were stably transmitted and expressed VH segments that recombined with endogenous mouse sequences, and mice exhibited normal B cell development. Upon immunization, human VH-expressing B cells underwent class-switch recombination and somatic hypermutation, secreting antigen-specific antibodies. We demonstrated modular IgH humanization by replacing endogenous mouse diversity and joining (DH-JH) segments with human sequences, producing V(D)J recombination and diverse antibodies. Unlike traditional methods requiring more than a year, this approach enables the generation and validation of mice carrying large genomic insertions within 8 weeks.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":" ","pages":"2334-2350.e8"},"PeriodicalIF":30.6,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13361002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148420991","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

Disease-associated microglia adopt stage-specific phenotypes that regulate T cell fate and immunity in glioma. 在胶质瘤中，疾病相关的小胶质细胞采用调节T细胞命运和免疫的阶段特异性表型。

IF 30.6 1区医学

Immunity Pub Date : 2026-08-11 Epub Date: 2026-07-24 DOI: 10.1016/j.immuni.2026.06.024

Jiawen Qian, Chen Wang, Yi Zhang, Congwen Li, Yingying Zeng, Shuangyan Zhang, Fei Gao, Yiwen Zhu, Peiliang Cai, Zhongyuan Zhang, Yanan Hu, Xiaotong Yu, Benoit Kloeckner, Marco Moreira, Yuedi Wang, Bo Wang, Chujun Julia Zhao, Dan Zhang, Xi Chen, Shang Liu, Auriane Coutansais, Huangmijia Zhuang, Ronghua Liu, Feifei Luo, Liang Wu, Claudia Pasqualini, Yihua Chen, Xinyan Li, Mingfang Lu, Ziyi Li, Wei Guo, Svetoslav Chakarov, Zhaoyuan Liu, Bing Su, Rui Zhao, Yiwei Chu, Florent Ginhoux

{"title":"Disease-associated microglia adopt stage-specific phenotypes that regulate T cell fate and immunity in glioma.","authors":"Jiawen Qian, Chen Wang, Yi Zhang, Congwen Li, Yingying Zeng, Shuangyan Zhang, Fei Gao, Yiwen Zhu, Peiliang Cai, Zhongyuan Zhang, Yanan Hu, Xiaotong Yu, Benoit Kloeckner, Marco Moreira, Yuedi Wang, Bo Wang, Chujun Julia Zhao, Dan Zhang, Xi Chen, Shang Liu, Auriane Coutansais, Huangmijia Zhuang, Ronghua Liu, Feifei Luo, Liang Wu, Claudia Pasqualini, Yihua Chen, Xinyan Li, Mingfang Lu, Ziyi Li, Wei Guo, Svetoslav Chakarov, Zhaoyuan Liu, Bing Su, Rui Zhao, Yiwei Chu, Florent Ginhoux","doi":"10.1016/j.immuni.2026.06.024","DOIUrl":"10.1016/j.immuni.2026.06.024","url":null,"abstract":"Malignant gliomas are lethal brain tumors characterized by profound local immunosuppression and a radically remodeled myeloid landscape. Although these tumors mobilize resident microglia and infiltrating monocyte-derived macrophages, the mechanisms governing their phenotypic convergence and diversification remain elusive. Here, we integrated single-cell profiling and spatial transcriptomics of glioma-associated microglia in the GL261 model. We identified distinct microglial states that aligned with tumor architecture, most notably Cst7-expressing disease-associated microglia (DAMs) that aggregated at the tumor invasive margin and exhibited a conserved transcriptional signature shared across various central nervous system pathologies. Interferon-γ and toll-like receptor signaling sequentially tuned stage-specific DAM features, including transient MHC-II expression and sustained PD-L1 upregulation, thereby recalibrating the local immune equilibrium by reshaping bidirectional DAM-T cell interactions during glioma progression. Our findings highlight microglial state transitions as a stage-specific layer of immune regulation in glioma that shapes T cell fate and support targeting microglial plasticity to rebalance anti-tumor immunity.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":" ","pages":"2299-2316.e7"},"PeriodicalIF":30.6,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148584004","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

Environmentally induced cell stiffening shapes metastatic site selection by tuning the immune vulnerability of cancer cells. 环境诱导的细胞硬化通过调节癌细胞的免疫脆弱性来形成转移位点选择。

IF 30.6 1区医学

Immunity Pub Date : 2026-08-11 Epub Date: 2026-07-28 DOI: 10.1016/j.immuni.2026.06.025

Yassmin A Elbanna, Maria Tello-Lafoz, Aliya Holland, Ye Zhang, Chengyuan Li, Seema Amin, Zhenghan Wang, Jun-Goo Kwak, Alexandrina Yakimov, Anastasiia Vaska, Esther Lee, Myra Dada, Samuel Vayner, Sarah M Duquette, Young Hun Kim, Jahkwaun Budhai, Ning Fan, Erik Ladewig, Tejus A Bale, Benjamin Y Winer, Kenny K H Yu, Joan Massagué, Christina Leslie, Jungwoo Lee, Ori Barzilai, Scott R Manalis, Morgan Huse

{"title":"Environmentally induced cell stiffening shapes metastatic site selection by tuning the immune vulnerability of cancer cells.","authors":"Yassmin A Elbanna, Maria Tello-Lafoz, Aliya Holland, Ye Zhang, Chengyuan Li, Seema Amin, Zhenghan Wang, Jun-Goo Kwak, Alexandrina Yakimov, Anastasiia Vaska, Esther Lee, Myra Dada, Samuel Vayner, Sarah M Duquette, Young Hun Kim, Jahkwaun Budhai, Ning Fan, Erik Ladewig, Tejus A Bale, Benjamin Y Winer, Kenny K H Yu, Joan Massagué, Christina Leslie, Jungwoo Lee, Ori Barzilai, Scott R Manalis, Morgan Huse","doi":"10.1016/j.immuni.2026.06.025","DOIUrl":"10.1016/j.immuni.2026.06.025","url":null,"abstract":"Metastatic microenvironments vary widely not only in their biochemical composition but also in their mechanical properties. Here, we examined how the mechanical rigidity of the metastatic niche affects metastases seeding and the local efficacy of antitumor immunosurveillance. Cancer cells stiffened in response to increasing environmental rigidity, a biophysical change that mechanically sensitized them to killing by cytotoxic lymphocytes. In immunodeficient mice, rigidity sensing by cancer cells yielded robust bone colonization, accompanied by marked stiffening of the cancer cells themselves. Conversely, in immunocompetent hosts, stiffer cancer cells were selectively eliminated, and bone metastasis was suppressed. In patients, metastatic cell stiffness was associated directly with environmental rigidity and inversely with immune infiltration. Expression of Spp1, encoding the secreted glycoprotein osteopontin, defined a subset of cancer cells that expanded in the bone, and deletion of Spp1 limited environmentally induced cancer cell stiffening, bone colonization, and immune vulnerability. Thus, environmental mechanosensing regulates both metastases seeding and antitumor immunity, providing an immunological basis for metastatic site selection.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":" ","pages":"2317-2333.e8"},"PeriodicalIF":30.6,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13484358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148602247","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

MEK-dependent bioenergetic demand drives terminal CD8⁺ T cell exhaustion. mek依赖性生物能量需求驱动末端CD8+ T细胞耗竭。

IF 30.6 1区医学

Immunity Pub Date : 2026-08-11 Epub Date: 2026-07-13 DOI: 10.1016/j.immuni.2026.06.012

Tanmana Mitra, Jahan Rahman, Madeline Hwee, Yan-Ting Chen, Ruben Jose Jesus Faustino Ramos, Hui Liu, Travis Hartman, Justin Cross, Miguel de Jesus, Morgan Huse, Valerie Longo, Pat Zanzonico, Santosha A Vardhana

{"title":"MEK-dependent bioenergetic demand drives terminal CD8+ T cell exhaustion.","authors":"Tanmana Mitra, Jahan Rahman, Madeline Hwee, Yan-Ting Chen, Ruben Jose Jesus Faustino Ramos, Hui Liu, Travis Hartman, Justin Cross, Miguel de Jesus, Morgan Huse, Valerie Longo, Pat Zanzonico, Santosha A Vardhana","doi":"10.1016/j.immuni.2026.06.012","DOIUrl":"10.1016/j.immuni.2026.06.012","url":null,"abstract":"Loss of mitochondrial function promotes CD8+ T cell dysfunction during persistent antigen encounter. Here, we examined the pathways whereby chronic antigen stimulation leads to metabolic dysfunction. Chronic T cell receptor (TCR) engagement increased ATP demand, leading to mitochondrial NADH accumulation, accumulation of reactive oxygen species, and subsequent mitochondrial dysfunction. Among TCR-dependent proximal signaling components, inhibiting the kinase MEK uniquely reduced nutrient uptake and mitochondrial NADH accumulation while restoring proliferation. Accordingly, MEK inhibition during chronic TCR stimulation reduced terminal T cell exhaustion. Mechanistically, chronic MEK activation in T cells drove ATP demand by increasing global protein synthesis rates in vitro and in vivo. MEK inhibition reversed chronic TCR stimulation-driven increases in RNA polymerase II C-terminal domain phosphorylation, reducing transcription rates at loci encoding effector- and terminal-exhaustion-associated genes while maintaining transcription of genes associated with T cell memory. Thus, MEK-dependent metabolic demand is a driver of T cell exhaustion, providing insight into how MEK inhibition enhances immunotherapy efficacy.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":" ","pages":"2215-2231.e9"},"PeriodicalIF":30.6,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13367423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148436407","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

Different lysosomal insults, one microglial fate. 不同的溶酶体损伤，一个小胶质细胞的命运。

IF 30.6 1区医学

Immunity Pub Date : 2026-08-11 DOI: 10.1016/j.immuni.2026.07.016

Baiping Wang, Hui Zheng

引用次数: 0

Bile acids in cancer: From metabolism to immunomodulation. 胆汁酸在癌症中的作用：从代谢到免疫调节。

IF 30.6 1区医学

Immunity Pub Date : 2026-08-11 Epub Date: 2026-07-29 DOI: 10.1016/j.immuni.2026.07.003

Qian Fang, Kai Markus Schneider

引用次数: 0

Peripheral vision: Treg cell induction in the gut. 周边视觉：肠道Treg细胞诱导。