Immunity最新文献_第10页

Autoantigen-specific CD4+ T cells acquire an exhausted phenotype and persist in human antigen-specific autoimmune diseases 自身抗原特异性 CD4+ T 细胞获得衰竭表型并在人类抗原特异性自身免疫疾病中持续存在

IF 32.4 1区医学

Immunity Pub Date : 2024-09-02 DOI: 10.1016/j.immuni.2024.08.005

Carina Saggau, Petra Bacher, Daniela Esser, Mahdi Rasa, Silja Meise, Nicola Mohr, Nora Kohlstedt, Andreas Hutloff, Sarah-Sophie Schacht, Justina Dargvainiene, Gabriela Rios Martini, Klarissa H. Stürner, Ina Schröder, Robert Markewitz, Johannes Hartl, Maria Hastermann, Ankelien Duchow, Patrick Schindler, Mareike Becker, Carolin Bautista, Alexander Scheffold

{"title":"Autoantigen-specific CD4+ T cells acquire an exhausted phenotype and persist in human antigen-specific autoimmune diseases","authors":"Carina Saggau, Petra Bacher, Daniela Esser, Mahdi Rasa, Silja Meise, Nicola Mohr, Nora Kohlstedt, Andreas Hutloff, Sarah-Sophie Schacht, Justina Dargvainiene, Gabriela Rios Martini, Klarissa H. Stürner, Ina Schröder, Robert Markewitz, Johannes Hartl, Maria Hastermann, Ankelien Duchow, Patrick Schindler, Mareike Becker, Carolin Bautista, Alexander Scheffold","doi":"10.1016/j.immuni.2024.08.005","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.08.005","url":null,"abstract":"Pro-inflammatory autoantigen-specific CD4+ T helper (auto-Th) cells are central orchestrators of autoimmune diseases (AIDs). We aimed to characterize these cells in human AIDs with defined autoantigens by combining human leukocyte antigen (HLA)-tetramer-based and activation-based multidimensional ex vivo analyses. In aquaporin4-antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD) patients, auto-Th cells expressed CD154, but proliferative capacity and pro-inflammatory cytokines were strongly reduced. Instead, exhaustion-associated co-inhibitory receptors were expressed together with FOXP3, the canonical regulatory T cell (Treg) transcription factor. Auto-Th cells responded in vitro to checkpoint inhibition and provided potent B cell help. Cells with the same exhaustion-like (ThEx) phenotype were identified in soluble liver antigen (SLA)-antibody-autoimmune hepatitis and BP180-antibody-positive bullous pemphigoid, AIDs of the liver and skin, respectively. While originally described in cancer and chronic infection, our data point to T cell exhaustion as a common mechanism of adaptation to chronic (self-)stimulation across AID types and link exhausted CD4+ T cells to humoral autoimmune responses, with implications for therapeutic targeting.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"30 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118151","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

Meningeal lymphatic function promotes oligodendrocyte survival and brain myelination 脑膜淋巴功能促进少突胶质细胞存活和大脑髓鞘化

IF 32.4 1区医学

Immunity Pub Date : 2024-08-31 DOI: 10.1016/j.immuni.2024.08.004

Sofia P. das Neves, Nickoleta Delivanoglou, Yingxue Ren, Chiara Starvaggi Cucuzza, Mateusz Makuch, Francisco Almeida, Guadalupe Sanchez, Megan J. Barber, Shanon Rego, Racquelle Schrader, Ayman H. Faroqi, Jean-Leon Thomas, Pamela J. McLean, Tiago Gil Oliveira, Sarosh R. Irani, Fredrik Piehl, Sandro Da Mesquita

{"title":"Meningeal lymphatic function promotes oligodendrocyte survival and brain myelination","authors":"Sofia P. das Neves, Nickoleta Delivanoglou, Yingxue Ren, Chiara Starvaggi Cucuzza, Mateusz Makuch, Francisco Almeida, Guadalupe Sanchez, Megan J. Barber, Shanon Rego, Racquelle Schrader, Ayman H. Faroqi, Jean-Leon Thomas, Pamela J. McLean, Tiago Gil Oliveira, Sarosh R. Irani, Fredrik Piehl, Sandro Da Mesquita","doi":"10.1016/j.immuni.2024.08.004","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.08.004","url":null,"abstract":"The precise neurophysiological changes prompted by meningeal lymphatic dysfunction remain unclear. Here, we showed that inducing meningeal lymphatic vessel ablation in adult mice led to gene expression changes in glial cells, followed by reductions in mature oligodendrocyte numbers and specific lipid species in the brain. These phenomena were accompanied by altered meningeal adaptive immunity and brain myeloid cell activation. During brain remyelination, meningeal lymphatic dysfunction provoked a state of immunosuppression in the brain that contributed to delayed spontaneous oligodendrocyte replenishment and axonal loss. The deficiencies in mature oligodendrocytes and neuroinflammation due to impaired meningeal lymphatic function were solely recapitulated in immunocompetent mice. Patients diagnosed with multiple sclerosis presented reduced vascular endothelial growth factor C in the cerebrospinal fluid, particularly shortly after clinical relapses, possibly indicative of poor meningeal lymphatic function. These data demonstrate that meningeal lymphatics regulate oligodendrocyte function and brain myelination, which might have implications for human demyelinating diseases.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"2014 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142101071","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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CD4+ T cells reactive to a hybrid peptide from insulin-chromogranin A adopt a distinct effector fate and are pathogenic in autoimmune diabetes 对胰岛素-色甘宁 A 混合肽产生反应的 CD4+ T 细胞具有独特的效应基因，是自身免疫性糖尿病的致病因子

IF 32.4 1区医学

Immunity Pub Date : 2024-08-29 DOI: 10.1016/j.immuni.2024.07.024

Jason S. Mitchell, Justin A. Spanier, Alexander J. Dwyer, Todd P. Knutson, Mohannad H. Alkhatib, Gina Qian, Matthew E. Weno, Yixin Chen, Zachary R. Shaheen, Christopher G. Tucker, Takashi O. Kangas, Milagros Silva Morales, Nubia Silva, Tsuneyasu Kaisho, Michael A. Farrar, Brian T. Fife

{"title":"CD4+ T cells reactive to a hybrid peptide from insulin-chromogranin A adopt a distinct effector fate and are pathogenic in autoimmune diabetes","authors":"Jason S. Mitchell, Justin A. Spanier, Alexander J. Dwyer, Todd P. Knutson, Mohannad H. Alkhatib, Gina Qian, Matthew E. Weno, Yixin Chen, Zachary R. Shaheen, Christopher G. Tucker, Takashi O. Kangas, Milagros Silva Morales, Nubia Silva, Tsuneyasu Kaisho, Michael A. Farrar, Brian T. Fife","doi":"10.1016/j.immuni.2024.07.024","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.07.024","url":null,"abstract":"T cell-mediated islet destruction is a hallmark of autoimmune diabetes. Here, we examined the dynamics and pathogenicity of CD4+ T cell responses to four different insulin-derived epitopes during diabetes initiation in non-obese diabetic (NOD) mice. Single-cell RNA sequencing of tetramer-sorted CD4+ T cells from the pancreas revealed that islet-antigen-specific T cells adopted a wide variety of fates and required XCR1+ dendritic cells for their activation. Hybrid-insulin C-chromogranin A (InsC-ChgA)-specific CD4+ T cells skewed toward a distinct T helper type 1 (Th1) effector phenotype, whereas the majority of insulin B chain and hybrid-insulin C-islet amyloid polypeptide-specific CD4+ T cells exhibited a regulatory phenotype and early or weak Th1 phenotype, respectively. InsC-ChgA-specific CD4+ T cells were uniquely pathogenic upon transfer, and an anti-InsC-ChgA:IAg7 antibody prevented spontaneous diabetes. Our findings highlight the heterogeneity of T cell responses to insulin-derived epitopes in diabetes and argue for the feasibility of antigen-specific therapies that blunts the response of pathogenic CD4+ T cells causing autoimmunity.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"19 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142090519","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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CD4+ T cells re-wire granuloma cellularity and regulatory networks to promote immunomodulation following Mtb reinfection CD4+ T细胞重新构建肉芽肿细胞性和调控网络，促进Mtb再感染后的免疫调节

IF 32.4 1区医学

Immunity Pub Date : 2024-08-29 DOI: 10.1016/j.immuni.2024.08.002

Joshua D. Bromley, Sharie Keanne C. Ganchua, Sarah K. Nyquist, Pauline Maiello, Michael Chao, H. Jacob Borish, Mark Rodgers, Jaime Tomko, Kara Kracinovsky, Douaa Mugahid, Son Nguyen, Qianchang Dennis Wang, Jacob M. Rosenberg, Edwin C. Klein, Hannah P. Gideon, Roisin Floyd-O’Sullivan, Bonnie Berger, Charles A. Scanga, Philana Ling Lin, Sarah M. Fortune, JoAnne L. Flynn

{"title":"CD4+ T cells re-wire granuloma cellularity and regulatory networks to promote immunomodulation following Mtb reinfection","authors":"Joshua D. Bromley, Sharie Keanne C. Ganchua, Sarah K. Nyquist, Pauline Maiello, Michael Chao, H. Jacob Borish, Mark Rodgers, Jaime Tomko, Kara Kracinovsky, Douaa Mugahid, Son Nguyen, Qianchang Dennis Wang, Jacob M. Rosenberg, Edwin C. Klein, Hannah P. Gideon, Roisin Floyd-O’Sullivan, Bonnie Berger, Charles A. Scanga, Philana Ling Lin, Sarah M. Fortune, JoAnne L. Flynn","doi":"10.1016/j.immuni.2024.08.002","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.08.002","url":null,"abstract":"Immunological priming—in the context of either prior infection or vaccination—elicits protective responses against subsequent Mycobacterium tuberculosis (Mtb) infection. However, the changes that occur in the lung cellular milieu post-primary Mtb infection and their contributions to protection upon reinfection remain poorly understood. Using clinical and microbiological endpoints in a non-human primate reinfection model, we demonstrated that prior Mtb infection elicited a long-lasting protective response against subsequent Mtb exposure and was CD4+ T cell dependent. By analyzing data from primary infection, reinfection, and reinfection-CD4+ T cell-depleted granulomas, we found that the presence of CD4+ T cells during reinfection resulted in a less inflammatory lung milieu characterized by reprogrammed CD8+ T cells, reduced neutrophilia, and blunted type 1 immune signaling among myeloid cells. These results open avenues for developing vaccines and therapeutics that not only target lymphocytes but also modulate innate immune cells to limit tuberculosis (TB) disease.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"125 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142090522","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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PD-1 signaling limits expression of phospholipid phosphatase 1 and promotes intratumoral CD8+ T cell ferroptosis PD-1 信号限制磷脂磷酸酶 1 的表达并促进瘤内 CD8+ T 细胞铁变态反应

IF 32.4 1区医学

Immunity Pub Date : 2024-08-28 DOI: 10.1016/j.immuni.2024.08.003

Yu Ping, Jiqi Shan, Haiming Qin, Feng Li, Jiao Qu, Ru Guo, Dong Han, Wei Jing, Yaqing Liu, Jinyan Liu, Zhangnan Liu, Jieyao Li, Dongli Yue, Feng Wang, Liping Wang, Bin Zhang, Bo Huang, Yi Zhang

{"title":"PD-1 signaling limits expression of phospholipid phosphatase 1 and promotes intratumoral CD8+ T cell ferroptosis","authors":"Yu Ping, Jiqi Shan, Haiming Qin, Feng Li, Jiao Qu, Ru Guo, Dong Han, Wei Jing, Yaqing Liu, Jinyan Liu, Zhangnan Liu, Jieyao Li, Dongli Yue, Feng Wang, Liping Wang, Bin Zhang, Bo Huang, Yi Zhang","doi":"10.1016/j.immuni.2024.08.003","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.08.003","url":null,"abstract":"The tumor microenvironment (TME) promotes metabolic reprogramming and dysfunction in immune cells. Here, we examined the impact of the TME on phospholipid metabolism in CD8+ T cells. In lung cancer, phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were lower in intratumoral CD8+ T cells than in circulating CD8+ T cells. Intratumoral CD8+ T cells exhibited decreased expression of phospholipid phosphatase 1 (PLPP1), which catalyzes PE and PC synthesis. T cell-specific deletion of Plpp1 impaired antitumor immunity and promoted T cell death by ferroptosis. Unsaturated fatty acids in the TME stimulated ferroptosis of Plpp1−/− CD8+ T cells. Mechanistically, programmed death-1 (PD-1) signaling in CD8+ T cells induced GATA1 binding to the promoter region Plpp1 and thereby suppressed Plpp1 expression. PD-1 blockade increased Plpp1 expression and restored CD8+ T cell antitumor function but did not rescue dysfunction of Plpp1−/− CD8+ T cells. Thus, PD-1 signaling regulates phospholipid metabolism in CD8+ T cells, with therapeutic implications for immunotherapy.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"146 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142085764","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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ZFP318 fuels memory B cells for success ZFP318 为记忆 B 细胞的成功提供动力

IF 32.4 1区医学

Immunity Pub Date : 2024-08-13 DOI: 10.1016/j.immuni.2024.07.017

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Wriggly woes: Helminths stirring up T cell trouble 蠕虫的烦恼：螺旋虫给 T 细胞带来麻烦

IF 32.4 1区医学

Immunity Pub Date : 2024-08-13 DOI: 10.1016/j.immuni.2024.07.014

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Hit me baby one more time…with microbial IPA 再打我一次宝贝......用微生物IPA

IF 32.4 1区医学

Immunity Pub Date : 2024-08-13 DOI: 10.1016/j.immuni.2024.07.007