Cellular &Molecular Immunology最新文献_第6页

Age-associated imbalance in immune cell regeneration varies across individuals and arises from a distinct subset of stem cells 与年龄相关的免疫细胞再生失衡现象因人而异，并由不同的干细胞亚群引起。

IF 21.8 1区医学

Cellular &Molecular Immunology Pub Date : 2024-10-24 DOI: 10.1038/s41423-024-01225-y

Anna Nogalska, Jiya Eerdeng, Samir Akre, Mary Vergel-Rodriguez, Yeachan Lee, Charles Bramlett, Adnan Y. Chowdhury, Bowen Wang, Colin G. Cess, Stacey D. Finley, Rong Lu

{"title":"Age-associated imbalance in immune cell regeneration varies across individuals and arises from a distinct subset of stem cells","authors":"Anna Nogalska, Jiya Eerdeng, Samir Akre, Mary Vergel-Rodriguez, Yeachan Lee, Charles Bramlett, Adnan Y. Chowdhury, Bowen Wang, Colin G. Cess, Stacey D. Finley, Rong Lu","doi":"10.1038/s41423-024-01225-y","DOIUrl":"10.1038/s41423-024-01225-y","url":null,"abstract":"The age-associated decline in immunity manifests as imbalanced adaptive and innate immune cells, which originate from the aging of the stem cells that sustain their regeneration. Aging variation across individuals is well recognized, but its mechanism remains unclear. Here, we used high-throughput single-cell technologies to compare mice of the same chronological age that exhibited early or delayed immune aging phenotypes. We found that some hematopoietic stem cells (HSCs) in early aging mice upregulated genes related to aging, myeloid differentiation, and stem cell proliferation. Delayed aging was instead associated with genes involved in stem cell regulation and the response to external signals. These molecular changes align with shifts in HSC function. We found that the lineage biases of 30% to 40% of the HSC clones shifted with age. Moreover, their lineage biases shifted in opposite directions in mice exhibiting an early or delayed aging phenotype. In early aging mice, the HSC lineage bias shifted toward the myeloid lineage, driving the aging phenotype. In delayed aging mice, HSC lineage bias shifted toward the lymphoid lineage, effectively counteracting aging progression. Furthermore, the anti-aging HSC clones did not increase lymphoid production but instead decreased myeloid production. Additionally, we systematically quantified the frequency of various changes in HSC differentiation and their roles in driving the immune aging phenotype. Taken together, our findings suggest that temporal variation in the aging of immune cell regeneration among individuals primarily arises from differences in the myelopoiesis of a distinct subset of HSCs. Therefore, interventions to delay aging may be possible by targeting a subset of stem cells.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"21 12","pages":"1459-1473"},"PeriodicalIF":21.8,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41423-024-01225-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496078","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

Ubiquitin regulatory X (UBX) domain-containing protein 6 is essential for autophagy induction and inflammation control in macrophages 含泛素调节 X（UBX）结构域的蛋白 6 对巨噬细胞的自噬诱导和炎症控制至关重要。

IF 21.8 1区医学

Cellular &Molecular Immunology Pub Date : 2024-10-23 DOI: 10.1038/s41423-024-01222-1

Young Jae Kim, Sung-Gwon Lee, So Young Park, Sang Min Jeon, Soo In Kim, Kyung Tae Kim, Taylor Roh, Sang-Hee Lee, Min Joung Lee, Jinyoung Lee, Hyeon Ji Kim, So Eui Lee, Jin Kyung Kim, Jun Young Heo, In Soo Kim, Chungoo Park, Seungwha Paik, Eun-Kyeong Jo

{"title":"Ubiquitin regulatory X (UBX) domain-containing protein 6 is essential for autophagy induction and inflammation control in macrophages","authors":"Young Jae Kim, Sung-Gwon Lee, So Young Park, Sang Min Jeon, Soo In Kim, Kyung Tae Kim, Taylor Roh, Sang-Hee Lee, Min Joung Lee, Jinyoung Lee, Hyeon Ji Kim, So Eui Lee, Jin Kyung Kim, Jun Young Heo, In Soo Kim, Chungoo Park, Seungwha Paik, Eun-Kyeong Jo","doi":"10.1038/s41423-024-01222-1","DOIUrl":"10.1038/s41423-024-01222-1","url":null,"abstract":"Ubiquitin regulatory X (UBX) domain-containing protein 6 (UBXN6) is an essential cofactor for the activity of the valosin-containing protein p97, an adenosine triphosphatase associated with diverse cellular activities. Nonetheless, its role in cells of the innate immune system remains largely unexplored. In this study, we report that UBXN6 is upregulated in humans with sepsis and may serve as a pivotal regulator of inflammatory responses via the activation of autophagy. Notably, the upregulation of UBXN6 in sepsis patients was negatively correlated with inflammatory gene profiles but positively correlated with the expression of Forkhead box O3, an autophagy-driving transcription factor. Compared with those of control mice, the macrophages of mice subjected to myeloid cell-specific UBXN6 depletion exhibited exacerbated inflammation, increased mitochondrial oxidative stress, and greater impairment of autophagy and endoplasmic reticulum-associated degradation pathways. UBXN6-deficient macrophages also exhibited immunometabolic remodeling, characterized by a shift to aerobic glycolysis and elevated levels of branched-chain amino acids. These metabolic shifts amplify mammalian target of rapamycin pathway signaling, in turn reducing the nuclear translocation of the transcription factor EB and impairing lysosomal biogenesis. Together, these data reveal that UBXN6 serves as an activator of autophagy and regulates inflammation to maintain immune system suppression during human sepsis.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"21 12","pages":"1441-1458"},"PeriodicalIF":21.8,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41423-024-01222-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496080","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}

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Kynurenine-AhR reduces T-cell infiltration and induces a delayed T-cell immune response by suppressing the STAT1-CXCL9/CXCL10 axis in tuberculosis 犬尿氨酸-AhR 通过抑制 STAT1-CXCL9/CXCL10 轴，减少结核病中的 T 细胞浸润并诱导延迟的 T 细胞免疫反应。

IF 21.8 1区医学

Cellular &Molecular Immunology Pub Date : 2024-10-22 DOI: 10.1038/s41423-024-01230-1

Xin Liu, Mengjie Yang, Ping Xu, Mingwei Du, Shanshan Li, Jin Shi, Qiang Li, Jinfeng Yuan, Yu Pang

{"title":"Kynurenine-AhR reduces T-cell infiltration and induces a delayed T-cell immune response by suppressing the STAT1-CXCL9/CXCL10 axis in tuberculosis","authors":"Xin Liu, Mengjie Yang, Ping Xu, Mingwei Du, Shanshan Li, Jin Shi, Qiang Li, Jinfeng Yuan, Yu Pang","doi":"10.1038/s41423-024-01230-1","DOIUrl":"10.1038/s41423-024-01230-1","url":null,"abstract":"Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), is a critical global health issue that is complicated by the ability of the pathogen to delay the host’s T-cell immune response. This delay in T-cell recruitment to the site of infection is a pivotal survival strategy for Mtb, allowing it to establish a persistent chronic infection. To investigate the underlying mechanisms, this study focused on Mtb’s exploitation of host tryptophan metabolism. Mtb upregulates indoleamine 2,3-dioxygenase 1 (IDO1) in inflammatory macrophages, thereby increasing kynurenine (Kyn) production. Kyn then activates the aryl hydrocarbon receptor (AhR), leading to the upregulation of suppressor of cytokine signaling 3 and subsequent inhibition of the JAK-STAT1 signaling pathway. This results in reduced secretion of the chemokines CXCL9 and CXCL10, which are crucial for T-cell recruitment to the lungs. Supported by in vivo mouse models, our findings reveal that disrupting this pathway through AhR knockout significantly enhances T-cell infiltration and activity, thereby undermining Mtb-induced immunosuppression. In contrast, additional Kyn injection obviously inhibited T-cell infiltration and activity. These results highlight potential therapeutic targets of AhR and IDO1, offering new avenues for enhancing the host immune response against tuberculosis and guiding future vaccine development efforts.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"21 12","pages":"1426-1440"},"PeriodicalIF":21.8,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41423-024-01230-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496079","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

No more LAGging behind PD-1: uncovering the unique role of LAG-3 in T-cell exhaustion PD-1背后不再有LAG：揭示LAG-3在T细胞衰竭中的独特作用。

IF 21.8 1区医学

Cellular &Molecular Immunology Pub Date : 2024-10-21 DOI: 10.1038/s41423-024-01227-w

Yunju Jo, Hyung-seung Jin, Yoon Park

引用次数: 0

CD30 influences germinal center B-cell dynamics and the expansion of IgG1-switched B cells CD30 影响生殖中心 B 细胞的动态和 IgG1 开关 B 细胞的扩增。

IF 21.8 1区医学

Cellular &Molecular Immunology Pub Date : 2024-10-17 DOI: 10.1038/s41423-024-01219-w

Yan Wang, Ursula Rambold, Petra Fiedler, Tea Babushku, Claas L. Tapken, Kai P. Hoefig, Thomas P. Hofer, Heiko Adler, Ali Önder Yildirim, Lothar J. Strobl, Ursula Zimber-Strobl

{"title":"CD30 influences germinal center B-cell dynamics and the expansion of IgG1-switched B cells","authors":"Yan Wang, Ursula Rambold, Petra Fiedler, Tea Babushku, Claas L. Tapken, Kai P. Hoefig, Thomas P. Hofer, Heiko Adler, Ali Önder Yildirim, Lothar J. Strobl, Ursula Zimber-Strobl","doi":"10.1038/s41423-024-01219-w","DOIUrl":"10.1038/s41423-024-01219-w","url":null,"abstract":"Initially, identified as a Hodgkin lymphoma marker, CD30 was subsequently detected on a subset of human B cells within and around germinal centers (GCs). While CD30 expression is typically restricted to a few B cells, expansion of CD30-expressing B cells occurs in certain immune disorders and during viral infections. The role of CD30 in B cells remains largely unclear. To address this gap in knowledge, we established a conditional CD30-knockin mouse strain. In these mice, B-cell-specific CD30 expression led to a normal B-cell phenotype in young mice, but most aged mice exhibited significant expansion of B cells, T cells and myeloid cells and increased percentages of GC B cells and IgG1-switched cells. This may be driven by the expansion of CD4+ senescence-associated T cells and T follicular helper cells, which partially express CD30-L (CD153) and may stimulate CD30-expressing B cells. Inducing CD30 expression in antigen-activated B cells accelerates the GC reaction and augments plasma cell differentiation, possibly through the posttranscriptional upregulation of CXCR4. Furthermore, CD30 expression in GC B cells promoted the expansion of IgG1-switched cells, which displayed either a GC or memory-like B-cell phenotype, with abnormally high IgG1 levels compared with those in controls. These findings shed light on the role of CD30 signaling in GC B cells and suggest that elevated CD30+ B-cell numbers lead to pathological lymphocyte activation and proliferation.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"21 12","pages":"1410-1425"},"PeriodicalIF":21.8,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41423-024-01219-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459284","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

Immunotherapy for glioblastoma: current state, challenges, and future perspectives 胶质母细胞瘤的免疫疗法：现状、挑战和未来展望。

IF 21.8 1区医学

Cellular &Molecular Immunology Pub Date : 2024-10-15 DOI: 10.1038/s41423-024-01226-x

Yang Liu, Fei Zhou, Heba Ali, Justin D. Lathia, Peiwen Chen

引用次数: 0

Macrophage diversity in cancer dissemination and metastasis 癌症传播和转移中的巨噬细胞多样性

IF 21.8 1区医学

Cellular &Molecular Immunology Pub Date : 2024-10-14 DOI: 10.1038/s41423-024-01216-z

Alberto Mantovani, Federica Marchesi, Diletta Di Mitri, Cecilia Garlanda

引用次数: 0

Regulation of CD8+ T cells by lipid metabolism in cancer progression 癌症进展过程中脂质代谢对 CD8+ T 细胞的调控。

IF 21.8 1区医学

Cellular &Molecular Immunology Pub Date : 2024-10-14 DOI: 10.1038/s41423-024-01224-z

Yong Tang, Ziqing Chen, Qianying Zuo, Yibin Kang

{"title":"Regulation of CD8+ T cells by lipid metabolism in cancer progression","authors":"Yong Tang, Ziqing Chen, Qianying Zuo, Yibin Kang","doi":"10.1038/s41423-024-01224-z","DOIUrl":"10.1038/s41423-024-01224-z","url":null,"abstract":"Dysregulation of lipid metabolism is a key characteristic of the tumor microenvironment, where tumor cells utilize lipids for proliferation, survival, metastasis, and evasion of immune surveillance. Lipid metabolism has become a critical regulator of CD8+ T-cell-mediated antitumor immunity, with excess lipids in the tumor microenvironment impeding CD8+ T-cell activities. Considering the limited efficacy of immunotherapy in many solid tumors, targeting lipid metabolism to enhance CD8+ T-cell effector functions could significantly improve immunotherapy outcomes. In this review, we examine recent findings on how lipid metabolic processes, including lipid uptake, synthesis, and oxidation, regulate CD8+ T cells within tumors. We also assessed the impact of different lipids on CD8+ T-cell-mediated antitumor immunity, with a particular focus on how lipid metabolism affects mitochondrial function in tumor-infiltrating CD8+ T cells. Furthermore, as cancer is a systemic disease, we examined systemic factors linking lipid metabolism to CD8+ T-cell effector function. Finally, we summarize current therapeutic approaches that target lipid metabolism to increase antitumor immunity and enhance immunotherapy. Understanding the molecular and functional interplay between lipid metabolism and CD8+ T cells offers promising therapeutic opportunities for cancer treatment.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"21 11","pages":"1215-1230"},"PeriodicalIF":21.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41423-024-01224-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459288","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

Silencing of SIRPα enhances the antitumor efficacy of CAR-M in solid tumors 沉默 SIRPα 可增强 CAR-M 在实体瘤中的抗肿瘤疗效。

IF 21.8 1区医学

Cellular &Molecular Immunology Pub Date : 2024-10-08 DOI: 10.1038/s41423-024-01220-3

Han Zhang, Yi Huo, Wenjing Zheng, Peng Li, Hui Li, Lingling Zhang, Longqi Sa, Yang He, Zihao Zhao, Changhong Shi, Lequn Shan, Angang Yang, Tao Wang

{"title":"Silencing of SIRPα enhances the antitumor efficacy of CAR-M in solid tumors","authors":"Han Zhang, Yi Huo, Wenjing Zheng, Peng Li, Hui Li, Lingling Zhang, Longqi Sa, Yang He, Zihao Zhao, Changhong Shi, Lequn Shan, Angang Yang, Tao Wang","doi":"10.1038/s41423-024-01220-3","DOIUrl":"10.1038/s41423-024-01220-3","url":null,"abstract":"The potential of macrophage-mediated phagocytosis as a cancer treatment is promising. Blocking the CD47–SIRPα interaction with a CD47-specific antibody significantly enhances macrophage phagocytosis. However, concerns regarding their toxicity to nontumor cells remain substantial. Here, we engineered chimeric antigen receptor macrophages (CAR-Ms) by fusing a humanized single-chain variable fragment with FcγRIIa and integrating short hairpin RNA to silence SIRPα, thereby disrupting the CD47–SIRPα signaling pathway. These modified CAR-shSIRPα-M cells exhibited an M1-like phenotype, superior phagocytic function, substantial cytotoxic effects on HER2-positive tumor cells, and the ability to eliminate patient-derived organoids. In vivo, CAR-M cells significantly inhibited tumor growth and prolonged survival in tumor-bearing mice. Notably, CAR-shSIRPα-M cells enhanced cytotoxic T-cell infiltration into tumors, thereby enhancing the antitumor response in both the humanized immune system mouse model and immunocompetent mice. Mechanistically, SIRPα inhibition activated inflammatory pathways and the cGAS-STING signaling cascade in CAR-M cells, leading to increased production of proinflammatory cytokines, reactive oxygen species, and nitric oxide, thereby enhancing their antitumor effects. These findings underscore the potential of SIRPα inhibition as a novel strategy to increase the antitumor efficacy of CAR-M cells in cancer immunotherapy, particularly against solid tumors.","PeriodicalId":9950,"journal":{"name":"Cellular &Molecular Immunology","volume":"21 11","pages":"1335-1349"},"PeriodicalIF":21.8,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41423-024-01220-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388450","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

The TET3 inflammasome senses unique long HSV-1 proteins for virus particle budding from the nucleus TET3 炎症体感知独特的 HSV-1 长蛋白，以便病毒粒子从细胞核出芽。

IF 21.8 1区医学

Cellular &Molecular Immunology Pub Date : 2024-10-08 DOI: 10.1038/s41423-024-01221-2

Qiannv Liu, Weitao Li, Yan Qian, Chunlei Wang, Chun Kong, Mengqian Li, Liangliang Sun, Lang Sun, Yanli Pang, Changtao Jiang, Shuo Wang, Pengyan Xia

引用次数: 0