Immunity & Ageing最新文献

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Neuroimmunology and ageing – the state of the art 神经免疫学与老龄化--最新进展
IF 7.9 2区 医学
Immunity & Ageing Pub Date : 2024-01-10 DOI: 10.1186/s12979-024-00411-w
Moisés E. Bauer, Graham Pawelec, Roberto Paganelli
{"title":"Neuroimmunology and ageing – the state of the art","authors":"Moisés E. Bauer, Graham Pawelec, Roberto Paganelli","doi":"10.1186/s12979-024-00411-w","DOIUrl":"https://doi.org/10.1186/s12979-024-00411-w","url":null,"abstract":"<p>For decades, the central nervous system (CNS) was known as an immune-privileged site. This concept was formulated based on experimental studies that demonstrated that, unlike what was observed in peripheral organs, skin grafts were not rejected when transplanted into the brain parenchyma. The presence of the blood-brain barrier (BBB), capable of selectively regulating the entry of molecules and cells from the bloodstream into the brain parenchyma, and the absence of conventional lymphatic vessels contributed to reinforcing this concept [1]. However, meningeal lymphatic vessels in the dura mater and, more recently, glymphatic vessels have raised questions about the dogma of the CNS as an immune-privileged site [2, 3]. The CNS has thus adopted mechanisms that enable communication with the immune system, which is crucial for a healthy brain.</p><p>Recent studies highlight the borders of the CNS as pivotal sites of neuro-immune interactions. Under physiological conditions, characterized by the absence of leukocytes in the brain parenchyma, innate immune cells, such as macrophages, and adaptive immune cells, such as T and B cells, are present in meningeal regions, in the choroid plexus and perivascular spaces. In addition to actively participating in immune surveillance in the CNS, these cells contribute to the maintenance of brain homeostasis and may influence behavioural and cognitive responses [4, 5]. For instance, cytokines secreted by immune cells, localized at the brain borders, may change behaviour through modulation of neuronal activities in distinct brain regions [5]. Indeed, several T cell-related cytokines have been shown to modulate complex CNS functions, by inducing changes in neuronal physiology: interferon γ (IFN-γ) alters sociability [6], IL-17 maintains anxiety and spatial learning [7], and IL-4 regulates learning and memory [8].</p><p>Inflammaging is a low level pro-inflammatory state which is believed to be a major contributor to biological aging which underlies many age-associated diseases. Peripheral inflammation significantly affects brain function and contributes to the development of several neurological disorders. Changes in interactions between the CNS and the immune system, such as those observed during ageing, could predispose to the development of neurodegenerative and neuropsychiatric diseases. Both ageing and neuropsychiatric disorders of older adults seem to converge on the pathogenetic role of inflammation, hence the notion of neuroinflammation. Increasing evidence indicates the role of neuroinflammation in age-related neurodegenerative diseases, such as Alzheimer’s Disease (AD) and Parkinson’s disease (PD). The neuropathological features of these diseases include aggregation and accumulation of intracellular and/or extracellular proteins that are associated with neuronal loss in specific regions of the brain. Furthermore, proliferation and activation of glial cells (i.e., “gliosis”) are well established in these di","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":null,"pages":null},"PeriodicalIF":7.9,"publicationDate":"2024-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139414187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Inflammatory markers and physical frailty: towards clinical application. 炎症标志物与体质虚弱:走向临床应用。
IF 7.9 2区 医学
Immunity & Ageing Pub Date : 2024-01-06 DOI: 10.1186/s12979-023-00410-3
Yiming Pan, Lina Ma
{"title":"Inflammatory markers and physical frailty: towards clinical application.","authors":"Yiming Pan, Lina Ma","doi":"10.1186/s12979-023-00410-3","DOIUrl":"10.1186/s12979-023-00410-3","url":null,"abstract":"<p><p>Global population aging poses a tremendous burden on the health care system worldwide. Frailty is associated with decreased physical reserve and is considered an important indicator of adverse events in the older population. Therefore, there is growing interest in the early diagnosis and intervention of frailty, but the cellular mechanisms responsible for frailty are still not completely understood. Chronic inflammation is related to decreased physical function and increased disease risk. Additionally, multiple human and animal studies suggest that inflammation probably plays the largest role in contributing to frailty. Some inflammatory markers have been proposed to predict physical frailty. However, there are still large gaps in knowledge related to the clinical application of these markers in frail patients. Therefore, understanding the biological processes and identifying recognized and reliable markers are urgent and pivotal tasks for geriatricians. In the present review, we broadly summarize the inflammatory markers that may have potential diagnostic and therapeutic use, thereby translating them into health care for older people with frailty in the near future.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":null,"pages":null},"PeriodicalIF":7.9,"publicationDate":"2024-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10770917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139111343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Helicobacter pylori infection and Parkinson’s Disease: etiology, pathogenesis and levodopa bioavailability 幽门螺杆菌感染与帕金森病:病因、发病机制和左旋多巴生物利用度
IF 7.9 2区 医学
Immunity & Ageing Pub Date : 2024-01-02 DOI: 10.1186/s12979-023-00404-1
Bang-rong Wei, Yu-jia Zhao, Yu-feng Cheng, Chun Huang, Feng Zhang
{"title":"Helicobacter pylori infection and Parkinson’s Disease: etiology, pathogenesis and levodopa bioavailability","authors":"Bang-rong Wei, Yu-jia Zhao, Yu-feng Cheng, Chun Huang, Feng Zhang","doi":"10.1186/s12979-023-00404-1","DOIUrl":"https://doi.org/10.1186/s12979-023-00404-1","url":null,"abstract":"Parkinson’s disease (PD), a neurodegenerative disorder with an unknown etiology, is primarily characterized by the degeneration of dopamine (DA) neurons. The prevalence of PD has experienced a significant surge in recent years. The unidentified etiology poses limitations to the development of effective therapeutic interventions for this condition. Helicobacter pylori (H. pylori) infection has affected approximately half of the global population. Mounting evidences suggest that H. pylori infection plays an important role in PD through various mechanisms. The autotoxin produced by H. pylori induces pro-inflammatory cytokines release, thereby facilitating the occurrence of central inflammation that leads to neuronal damage. Simultaneously, H. pylori disrupts the equilibrium of gastrointestinal microbiota with an overgrowth of bacteria in the small intestinal known as small intestinal bacterial overgrowth (SIBO). This dysbiosis of the gut flora influences the central nervous system (CNS) through microbiome-gut-brain axis. Moreover, SIBO hampers levodopa absorption and affects its therapeutic efficacy in the treatment of PD. Also, H. pylori promotes the production of defensins to regulate the permeability of the blood-brain barrier, facilitating the entry of harmful factors into the CNS. In addition, H. pylori has been found to induce gastroparesis, resulting in a prolonged transit time for levodopa to reach the small intestine. H. pylori may exploit levodopa to facilitate its own growth and proliferation, or it can inflict damage to the gastrointestinal mucosa, leading to gastrointestinal ulcers and impeding levodopa absorption. Here, this review focused on the role of H. pylori infection in PD from etiology, pathogenesis to levodopa bioavailability.","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":null,"pages":null},"PeriodicalIF":7.9,"publicationDate":"2024-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139078395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Partial loss of Sorting Nexin 27 resembles age- and Down syndrome-associated T cell dysfunctions 分拣内毒素 27 的部分缺失与年龄和唐氏综合征相关的 T 细胞功能障碍相似
IF 7.9 2区 医学
Immunity & Ageing Pub Date : 2024-01-02 DOI: 10.1186/s12979-023-00402-3
Cristina Rodriguez-Rodriguez, Natalia González-Mancha, Ane Ochoa-Echeverría, Rosa Liébana, Isabel Merida
{"title":"Partial loss of Sorting Nexin 27 resembles age- and Down syndrome-associated T cell dysfunctions","authors":"Cristina Rodriguez-Rodriguez, Natalia González-Mancha, Ane Ochoa-Echeverría, Rosa Liébana, Isabel Merida","doi":"10.1186/s12979-023-00402-3","DOIUrl":"https://doi.org/10.1186/s12979-023-00402-3","url":null,"abstract":"Sorting Nexin 27 (SNX27)-retromer complex facilitates cargo recycling from endosomes to the plasma membrane. SNX27 downregulation in neurons, as the result of Trisomy 21 (T21), has been linked with cognitive deficits due to impairment of AMPA and NMDA receptor recycling. Studies in human T cell lines likewise demonstrated that SNX27 regulates the correct delivery of cargoes to the immune synapse limiting the activation of pro-inflammatory pathways. Nevertheless, the physiological consequences of partial SNX27 loss in T cell homeostasis are still unclear. In this study, we have explored the consequences of T cell specific partial SNX27 downregulation in mice. T cells with partial SNX27 deficiency show a marked deficit in the CD4+ T cell pool, a hallmark of aging in mice and humans, and a well-characterized comorbidity of individuals with Down syndrome (DS). When analyzed ex vivo, CD4+ T cells with partial SNX27 deletion demonstrate enhanced proliferation but diminished IL-2 production. In contrast, the CD8+ population show enhanced expression of pro-inflammatory cytokines and lytic enzymes. This mouse model supports the relevance of SNX27 in the organization of the immune synapse, previously described in cell lines, as well as in the control of T cell homeostasis. Individuals with DS experiment an acceleration of the aging process, which particularly affects the immune and central nervous systems. Thus, we hypothesize that reduced SNX27 expression in DS could contribute to the dysregulation of these systems and further research in SNX27 will shed light on the molecular factors underlying the phenotypes observed in people with DS and its contribution to aging.","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":null,"pages":null},"PeriodicalIF":7.9,"publicationDate":"2024-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139078394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
An aging-related immune landscape in the hematopoietic immune system 造血免疫系统中与衰老相关的免疫景观
IF 7.9 2区 医学
Immunity & Ageing Pub Date : 2024-01-02 DOI: 10.1186/s12979-023-00403-2
Jianjie Lv, Chun Zhang, Xiuxing Liu, Chenyang Gu, Yidan Liu, Yuehan Gao, Zhaohao Huang, Qi Jiang, Binyao Chen, Daquan He, Tianfu Wang, Zhuping Xu, Wenru Su
{"title":"An aging-related immune landscape in the hematopoietic immune system","authors":"Jianjie Lv, Chun Zhang, Xiuxing Liu, Chenyang Gu, Yidan Liu, Yuehan Gao, Zhaohao Huang, Qi Jiang, Binyao Chen, Daquan He, Tianfu Wang, Zhuping Xu, Wenru Su","doi":"10.1186/s12979-023-00403-2","DOIUrl":"https://doi.org/10.1186/s12979-023-00403-2","url":null,"abstract":"Aging is a holistic change that has a major impact on the immune system, and immunosenescence contributes to the overall progression of aging. The bone marrow is the most important hematopoietic immune organ, while the spleen, as the most important extramedullary hematopoietic immune organ, maintains homeostasis of the human hematopoietic immune system (HIS) in cooperation with the bone marrow. However, the overall changes in the HIS during aging have not been described. Here, we describe a hematopoietic immune map of the spleen and bone marrow of young and old mice using single-cell sequencing and flow cytometry techniques. We observed extensive, complex changes in the HIS during aging. Compared with young mice, the immune cells of aged mice showed a marked tendency toward myeloid differentiation, with the neutrophil population accounting for a significant proportion of this response. In this change, hypoxia-inducible factor 1-alpha (Hif1α) was significantly overexpressed, and this enhanced the immune efficacy and inflammatory response of neutrophils. Our research revealed that during the aging process, hematopoietic stem cells undergo significant changes in function and composition, and their polymorphism and differentiation abilities are downregulated. Moreover, we found that the highly responsive CD62L + HSCs were obviously downregulated in aging, suggesting that they may play an important role in the aging process. Overall, aging extensively alters the cellular composition and function of the HIS. These findings could potentially give high-dimensional insights and enable more accurate functional and developmental analyses as well as immune monitoring in HIS aging.","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":null,"pages":null},"PeriodicalIF":7.9,"publicationDate":"2024-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139078397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Blood circulating bacterial DNA in hospitalized old COVID-19 patients 住院的 COVID-19 老年患者血液中的循环细菌 DNA
IF 7.9 2区 医学
Immunity & Ageing Pub Date : 2023-12-18 DOI: 10.1186/s12979-023-00401-4
Robertina Giacconi, Patrizia D’Aquila, Maurizio Cardelli, Francesco Piacenza, Elisa Pierpaoli, Giada Sena, Mirko Di Rosa, Anna Rita Bonfigli, Roberta Galeazzi, Antonio Cherubini, Massimiliano Fedecostante, Riccardo Sarzani, Chiara Di Pentima, Piero Giordano, Roberto Antonicelli, Fabrizia Lattanzio, Giuseppe Passarino, Mauro Provinciali, Dina Bellizzi
{"title":"Blood circulating bacterial DNA in hospitalized old COVID-19 patients","authors":"Robertina Giacconi, Patrizia D’Aquila, Maurizio Cardelli, Francesco Piacenza, Elisa Pierpaoli, Giada Sena, Mirko Di Rosa, Anna Rita Bonfigli, Roberta Galeazzi, Antonio Cherubini, Massimiliano Fedecostante, Riccardo Sarzani, Chiara Di Pentima, Piero Giordano, Roberto Antonicelli, Fabrizia Lattanzio, Giuseppe Passarino, Mauro Provinciali, Dina Bellizzi","doi":"10.1186/s12979-023-00401-4","DOIUrl":"https://doi.org/10.1186/s12979-023-00401-4","url":null,"abstract":"Coronavirus disease COVID-19 is a heterogeneous condition caused by SARS-CoV-2 infection. Generally, it is characterized by interstitial pneumonia that can lead to impaired gas-exchange, acute respiratory failure, and death, although a complex disorder of multi-organ dysfunction has also been described. The pathogenesis is complex, and a variable combination of factors has been described in critically ill patients. COVID-19 is a particular risk for older persons, particularly those with frailty and comorbidities. Blood bacterial DNA has been reported in both physiological and pathological conditions and has been associated with some haematological and laboratory parameters but, to date, no study has characterized it in hospitalized old COVID-19 patients The present study aimed to establish an association between blood bacterial DNA (BB-DNA) and clinical severity in old COVID-19 patients. BB-DNA levels were determined, by quantitative real-time PCRs targeting the 16S rRNA gene, in 149 hospitalized older patients (age range 65–99 years) with COVID-19. Clinical data, including symptoms and signs of infection, frailty status, and comorbidities, were assessed. BB-DNA was increased in deceased patients compared to discharged ones, and Cox regression analysis confirmed an association between BB-DNA and in-hospital mortality. Furthermore, BB-DNA was positively associated with the neutrophil count and negatively associated with plasma IFN-alpha. Additionally, BB-DNA was associated with diabetes. The association of BB-DNA with mortality, immune-inflammatory parameters and diabetes in hospitalized COVID-19 patients suggests its potential role as a biomarker of unfavourable outcomes of the disease, thus it could be proposed as a novel prognostic marker in the assessment of acute COVID-19 disease.","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":null,"pages":null},"PeriodicalIF":7.9,"publicationDate":"2023-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138716098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 inter-link of ageing, cancer and immunity: findings from real-world retrospective study 老龄化、癌症和免疫力之间的相互联系:真实世界回顾性研究的发现
IF 7.9 2区 医学
Immunity & Ageing Pub Date : 2023-12-15 DOI: 10.1186/s12979-023-00399-9
Xiaomin Fu, Peng Qin, Fanghui Li, Huifang Zhu, Hongqin You, Yong Zhang, Benling Xu, Tiepeng Li, Fang Zhang, Lu Han, Lingdi Zhao, Baozhen Ma, Zibing Wang, Quanli Gao
{"title":"The inter-link of ageing, cancer and immunity: findings from real-world retrospective study","authors":"Xiaomin Fu, Peng Qin, Fanghui Li, Huifang Zhu, Hongqin You, Yong Zhang, Benling Xu, Tiepeng Li, Fang Zhang, Lu Han, Lingdi Zhao, Baozhen Ma, Zibing Wang, Quanli Gao","doi":"10.1186/s12979-023-00399-9","DOIUrl":"https://doi.org/10.1186/s12979-023-00399-9","url":null,"abstract":"Although the concept of declined immune function associated with cancer has been accepted extensively, real-world clinical studies focusing on analysis of the peripheral blood immune changes underlying ageing, immunity and cancer are scarce. In this case-control study, we retrospectively analysed 1375 cancer patients and enrolled 275 age and gender matched healthy individuals. Flow cytometry was conducted to assess the immune changes. Further analysis was examined by SPSS 17.0 and GraphPad Prism 9 software. Cancer patients showed obviously decreased CD3+ T, CD3+CD4+ Th, CD3+CD8+ CTL, CD19+ B, CD16+CD56+ NK cell counts and lower percentage of PD-1 (programmed cell death protein-1, PD-1) positive cells than healthy control (P < 0.0001). For cancer patients, the reference range of circulating percentage of PD-1+CD45+ cells, PD-1+CD3+ T cells, PD-1+CD3+CD4+ Th cells and PD-1+CD3+CD8+ CTL (Cytotoxic T Lymphocyte, CTL) were 11.2% (95% CI 10.8%-11.6%), 15.5% (95% CI 14.7%-16.0%), 15.4% (95% CI 14.9%-16.0%) and 14.5% (95% CI 14.0%-15.5%), respectively. Moreover, the reduction of CD3+ T, CD3+CD4+ Th, CD3+CD8+ CTL, CD19+ B cell counts accompanied with age and stage advancing (P < 0.05). CD16+CD56+ NK cells decreased with stage, but elevated in aged and male cancer patients (P < 0.05). Additionally, the percentage of PD-1 positive cells varied across cancer types, raised with age and stage. Head and neck, pancreatic, gynaecological and lung demonstrated a higher level of the percentage of PD-1 positive cells than melanoma, prostate, and breast cancer (P < 0.05). This study provides the reference range of the percentage of PD-1 positive cells on peripheral blood, confirms the decreased immune cells and a series of immune changes accompanying with cancer, expands our real world evidence to better understand the interactions of ageing, cancer and immunity. Moreover, the circulating percentage of PD-1 positive cells shows similar tumor type distribution with tumor mutational burden (TMB), supports that it maybe a potential predictive biomarker for immune checkpoint inhibitor therapy.","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":null,"pages":null},"PeriodicalIF":7.9,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138683521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
IL-17A promotes the progression of Alzheimer’s disease in APP/PS1 mice IL-17A 促进 APP/PS1 小鼠阿尔茨海默病的发展
IF 7.9 2区 医学
Immunity & Ageing Pub Date : 2023-12-14 DOI: 10.1186/s12979-023-00397-x
Min Cao, Jing Liu, Xiaomin Zhang, Yaqi Wang, Yuli Hou, Qiao Song, Yuting Cui, Yue Zhao, Peichang Wang
{"title":"IL-17A promotes the progression of Alzheimer’s disease in APP/PS1 mice","authors":"Min Cao, Jing Liu, Xiaomin Zhang, Yaqi Wang, Yuli Hou, Qiao Song, Yuting Cui, Yue Zhao, Peichang Wang","doi":"10.1186/s12979-023-00397-x","DOIUrl":"https://doi.org/10.1186/s12979-023-00397-x","url":null,"abstract":"Alzheimer’s disease (AD), which is the most common cause of dementia in elderly individuals, is a progressive neurodegenerative disorder. Neuroinflammation, which is an immune response that is activated by glial cells in the central nervous system, plays an important role in neurodegenerative diseases. Many studies have shown that interleukin-17A (IL-17A) plays an important role in AD, but research on the pathological effects of IL-17A on AD is limited. We report the effect of IL-17A on AD progression in APPswe/PS1dE9 (APP/PS1) mice, which are the most widely used AD model mice. The BV2 cell line, which is a microglial cell line derived from C57/BL6 mice, was used to establish a cell model to verify the role of IL-17A in neuroinflammation at the cellular level. The HT22 hippocampal neuronal cell line was used to investigate the relationship between IL-17A and Aβ deposition. In this research, we found that IL-17A promotes the progression of AD in the APP/PS1 mouse model. The role of IL-17A in neuroinflammation is related to tumour necrosis factor (TNF)-α. Circulating IL-17A stimulates the secretion of TNF-α by microglia through the Toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB signalling pathway, thus exacerbating neuroinflammation. In addition, intraperitoneal injection of IL-17A antibody (IL17Ab) significantly improved the cognitive function of APP/PS1 mice. IL-17A increased TNF-α levels in the brain and exacerbated neuroinflammation through the TLR4/NF-κB signalling pathway and microglial activation in APP/PS1 mice. Moreover, IL-17A promoted the progression of AD by enhancing neuroinflammation, inhibiting microglial phagocytosis, and promoting the deposition of β-amyloid 42 in AD model mice.","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":null,"pages":null},"PeriodicalIF":7.9,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138629061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 effect of metformin on senescence of T lymphocytes 二甲双胍对 T 淋巴细胞衰老的影响
IF 7.9 2区 医学
Immunity & Ageing Pub Date : 2023-12-12 DOI: 10.1186/s12979-023-00394-0
Jia Yang, Hai-Cheng Liu, Jian-Qing Zhang, Jian-Yong Zou, Xin Zhang, Wo-Ming Chen, Yong Gu, Hai Hong
{"title":"The effect of metformin on senescence of T lymphocytes","authors":"Jia Yang, Hai-Cheng Liu, Jian-Qing Zhang, Jian-Yong Zou, Xin Zhang, Wo-Ming Chen, Yong Gu, Hai Hong","doi":"10.1186/s12979-023-00394-0","DOIUrl":"https://doi.org/10.1186/s12979-023-00394-0","url":null,"abstract":"Immunosenescence occurs as people age, leading to an increased incidence of age-related diseases. The number of senescent T cells also rises with age. T cell senescence and immune response dysfunction can result in a decline in immune function, especially in anti-tumor immune responses. Metformin has been shown to have various beneficial effects on health, such as lowering blood sugar levels, reducing the risk of cancer development, and slowing down the aging process. However, the immunomodulatory effects of metformin on senescent T cells still need to be investigated. PBMCs isolation from different age population (n = 88); Flow Cytometry is applied to determine the phenotypic characterization of senescent T lymphocytes; intracellular staining is applied to determine the function of senescent T cells; Enzyme-Linked Immunosorbent Assay (ELISA) is employed to test the telomerase concentration. The RNA-seq analysis of gene expression associated with T cell senescence. The middle-aged group had the highest proportion of senescent T cells. We found that metformin could decrease the number of CD8 + senescent T cells. Metformin affects the secretion of SASP, inhibiting the secretion of IFN-γ in CD8 + senescent T cells. Furthermore, metformin treatment restrained the production of the proinflammatory cytokine IL-6 in lymphocytes. Metformin had minimal effects on Granzyme B secretion in senescent T cells, but it promoted the production of TNF-α in senescent T cells. Additionally, metformin increased the concentration of telomerase and the frequency of undifferentiated T cells. The results of RNA-seq showed that metformin promoted the expression of genes related to stemness and telomerase activity, while inhibiting the expression of DNA damage-associated genes. Our findings reveal that metformin could inhibit T cell senescence in terms of cell number, effector function, telomerase content and gene expression in middle-aged individuals, which may serve as a promising approach for preventing age-related diseases in this population.","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":null,"pages":null},"PeriodicalIF":7.9,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138576617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Senescence-associated secretory phenotypes in mesenchymal cells contribute to cytotoxic immune response in oral lichen planus. 间质细胞中与衰老相关的分泌表型有助于口腔扁平苔藓的细胞毒性免疫反应。
IF 7.9 2区 医学
Immunity & Ageing Pub Date : 2023-12-05 DOI: 10.1186/s12979-023-00400-5
Shogo Ijima, Yuki Saito, Sena Yamamoto, Kentaro Nagaoka, Taiki Iwamoto, Arisa Kita, Maki Miyajima, Tsukasa Sato, Akihiro Miyazaki, Takako S Chikenji
{"title":"Senescence-associated secretory phenotypes in mesenchymal cells contribute to cytotoxic immune response in oral lichen planus.","authors":"Shogo Ijima, Yuki Saito, Sena Yamamoto, Kentaro Nagaoka, Taiki Iwamoto, Arisa Kita, Maki Miyajima, Tsukasa Sato, Akihiro Miyazaki, Takako S Chikenji","doi":"10.1186/s12979-023-00400-5","DOIUrl":"10.1186/s12979-023-00400-5","url":null,"abstract":"<p><p>Oral lichen planus is a chronic inflammatory condition that adversely affects the oral mucosa; however, its etiology remains elusive. Consequently, therapeutic interventions for oral lichen planus are limited to symptomatic management. This study provides evidence of the accumulation of senescent mesenchymal cells, CD8 + T cells, and natural killer cells in patients with oral lichen planus. We profiled the patients' tissues using the National Center for Biotechnology Information Gene Expression Omnibus database and found that senescence-related genes were upregulated in these tissues by gene set enrichment analysis. Immunohistochemical analysis showed increased senescent mesenchymal cells in the subepithelial layer of patients with oral lichen planus. Single-cell RNA-seq data retrieved from the Gene Expression Omnibus database of patients with oral lichen planus revealed that mesenchymal cells were marked by the upregulation of senescence-related genes. Cell-cell communication analysis using CellChat showed that senescent mesenchymal cells significantly influenced CD8 + T cells and natural killer cells via CXCL12-CXCR4 signaling, which is known to activate and recruit CD8 + T cells and NK cells. Finally, in vitro assays demonstrated that the secretion of senescence-associated factors from mesenchymal cells stimulated the activation of T cells and natural killer cells and promoted epithelial cell senescence and cytotoxicity. These findings suggest that the accumulation of mesenchymal cells with senescence-associated secretory phenotype may be a key driver of oral lichen planus pathogenesis.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":null,"pages":null},"PeriodicalIF":7.9,"publicationDate":"2023-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10696703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138489019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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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