Immunity & Ageing最新文献

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Activating A1 adenosine receptor signaling boosts early pulmonary neutrophil recruitment in aged mice in response to Streptococcus pneumoniae infection 激活 A1 腺苷受体信号可促进老龄小鼠在肺炎链球菌感染时早期肺中性粒细胞的募集
IF 7.9 2区 医学
Immunity & Ageing Pub Date : 2024-06-05 DOI: 10.1186/s12979-024-00442-3
Shaunna R. Simmons, Sydney E. Herring, Essi Y.I Tchalla, Alexsandra P. Lenhard, Manmeet Bhalla, Elsa N. Bou Ghanem
{"title":"Activating A1 adenosine receptor signaling boosts early pulmonary neutrophil recruitment in aged mice in response to Streptococcus pneumoniae infection","authors":"Shaunna R. Simmons, Sydney E. Herring, Essi Y.I Tchalla, Alexsandra P. Lenhard, Manmeet Bhalla, Elsa N. Bou Ghanem","doi":"10.1186/s12979-024-00442-3","DOIUrl":"https://doi.org/10.1186/s12979-024-00442-3","url":null,"abstract":"Streptococcus pneumoniae (pneumococcus) is a leading cause of pneumonia in older adults. Successful control of pneumococci requires robust pulmonary neutrophil influx early in infection. However, aging is associated with aberrant neutrophil recruitment and the mechanisms behind that are not understood. Here we explored how neutrophil recruitment following pneumococcal infection changes with age and the host pathways regulating this. Following pneumococcal infection there was a significant delay in early neutrophil recruitment to the lungs of aged mice. Neutrophils from aged mice showed defects in trans-endothelial migration in vitro compared to young controls. To understand the pathways involved, we examined immune modulatory extracellular adenosine (EAD) signaling, that is activated upon cellular damage. Signaling through the lower affinity A2A and A2B adenosine receptors had no effect on neutrophil recruitment to infected lungs. In contrast, inhibition of the high affinity A1 receptor in young mice blunted neutrophil recruitment to the lungs following infection. A1 receptor inhibition decreased expression of CXCR2 on circulating neutrophils, which is required for trans-endothelial migration. Indeed, A1 receptor signaling on neutrophils was required for their ability to migrate across endothelial cells in response to infection. Aging was not associated with defects in EAD production or receptor expression on neutrophils. However, agonism of A1 receptor in aged mice rescued the early defect in neutrophil migration to the lungs and improved control of bacterial burden. This study suggests age-driven defects in EAD damage signaling can be targeted to rescue the delay in pulmonary neutrophil migration in response to bacterial pneumonia.","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":null,"pages":null},"PeriodicalIF":7.9,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141255244","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 role of blood related inflammatory factors on age-related macular degeneration (AMD) 血液相关炎症因子对老年性黄斑变性(AMD)的作用
IF 7.9 2区 医学
Immunity & Ageing Pub Date : 2024-06-05 DOI: 10.1186/s12979-024-00440-5
Habib Ojaghi, Shirin Poorsheykhian, Amin Najafi, Sohrab Iranpour
{"title":"The role of blood related inflammatory factors on age-related macular degeneration (AMD)","authors":"Habib Ojaghi, Shirin Poorsheykhian, Amin Najafi, Sohrab Iranpour","doi":"10.1186/s12979-024-00440-5","DOIUrl":"https://doi.org/10.1186/s12979-024-00440-5","url":null,"abstract":"Age-related macular degeneration (AMD) is a significant retinal disease that leads to irreversible low vision, particularly in developing countries. The variation in AMD prevalence among different racial groups and highlighted role of inflammation on disease pathology from previous studies which yielded in inconsistent findings, It seems to be of great importance to do more investigation in this field. This case control study involved 204 participants, divided into four groups of equal size (51 individuals per group). Three groups represented AMD cases of varying severity according to Beckman classification (3 groups) and one healthy control group. Sampling was conducted exhaustively until the desired sample size was reached. The control group comprised healthy individuals without any infectious or inflammatory systemic, ophthalmic disease. Blood samples were collected to measure inflammatory factors, including lymphocytes, monocytes, neutrophils, neutrophil-to-lymphocyte ratio (NLR), and C-reactive protein (CRP). Collected data were analyzed by statistical methods in SPSS version 21. Of the participants, 51% were women, and their ages ranged from 47 to 89 years (62.2 ± 8). According to multiple logistic regression analysis, age exhibited a statistically significant positive association with AMD severity (P = 0.038, odds ratio [OR] = 1.034). ANOVA results indicated a significant association between neutrophil count and AMD severity (P < 0.001). As the disease severity increased, the number of neutrophils decreased. The mean ± SD neutrophil counts for early, intermediate and advanced AMD were 3849 ± 800, 3702 ± 734, and 3342 ± 823, respectively. No statistically significant associations were found between lymphocyte count, monocyte count, neutrophil-to-lymphocyte ratio, CRP, and AMD. There was a significant relationship between the number of neutrophils in peripheral blood and the severity of AMD in study participants which needs more evaluation for the potential utility of this factor in the prognosis of AMD. There was not any significant relationship among the other factors and AMD.","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":null,"pages":null},"PeriodicalIF":7.9,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141255316","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
Chemokine receptor 7 contributes to T- and B-cell filtering in ageing bladder, cystitis and bladder cancer. 趋化因子受体 7 对老化膀胱、膀胱炎和膀胱癌中的 T 细胞和 B 细胞过滤有促进作用。
IF 7.9 2区 医学
Immunity & Ageing Pub Date : 2024-05-18 DOI: 10.1186/s12979-024-00432-5
Jiang Zhao, Xing Luo, Chengfei Yang, Xiao Yang, Min Deng, Bishao Sun, Jingzhen Zhu, Zongming Dong, Yangcai Wang, Jia Li, Xingliang Yang, Benyi Li, Xiangwei Wang, Ji Zheng
{"title":"Chemokine receptor 7 contributes to T- and B-cell filtering in ageing bladder, cystitis and bladder cancer.","authors":"Jiang Zhao, Xing Luo, Chengfei Yang, Xiao Yang, Min Deng, Bishao Sun, Jingzhen Zhu, Zongming Dong, Yangcai Wang, Jia Li, Xingliang Yang, Benyi Li, Xiangwei Wang, Ji Zheng","doi":"10.1186/s12979-024-00432-5","DOIUrl":"10.1186/s12979-024-00432-5","url":null,"abstract":"<p><strong>Background: </strong>Research has suggested significant correlations among ageing, immune microenvironment, inflammation and tumours. However, the relationships among ageing, immune microenvironment, cystitis and bladder urothelial carcinoma (BLCA) in the bladder have rarely been reported.</p><p><strong>Methods: </strong>Bladder single-cell and transcriptomic data from young and old mice were used for immune landscape analysis. Transcriptome, single-cell and The Cancer Genome Atlas Program datasets of BLCA and interstitial cystitis/bladder pain syndrome (IC/BPS) were used to analyse immune cell infiltration and molecular expression. Bladder tissues from mice, IC/BPS and BLCA were collected to validate the results.</p><p><strong>Results: </strong>Eight types of immune cells (macrophages, B-cells, dendritic cells, T-cells, monocytes, natural killer cells, γδ T-cells and ILC2) were identified in the bladder of mice. Aged mice bladder tissues had a significantly higher number of T-cells, γδ T-cells, ILC2 and B-cells than those in the young group (P < 0.05). Three types of T-cells (NK T-cells, γδ T-cells and naïve T-cells) and three types of B-cells (follicular B-cells, plasma and memory B-cells) were identified in aged mice bladder. Chemokine receptor 7 (CCR7) is highly expressed in aged bladder, IC/BPS and BLCA (P < 0.05). CCR7 is likely to be involved in T- and B-cell infiltration in aged bladder, IC/BPS and BLCA. Interestingly, the high CCR7 expression on BLCA cell membranes was a prognostic protective factor.</p><p><strong>Conclusions: </strong>In this study, we characterised the expression profiles of immune cells in bladder tissues of aged and young mice and demonstrated that CCR7-mediated T- and B-cell filtration contributes to the development of bladder ageing, IC/BPS and BLCA.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":null,"pages":null},"PeriodicalIF":7.9,"publicationDate":"2024-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11102276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140960135","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
The neutrophil to lymphocyte ratio associates with markers of Alzheimer's disease pathology in cognitively unimpaired elderly people. 中性粒细胞与淋巴细胞的比率与认知能力未受损的老年人阿尔茨海默病病理标志物有关。
IF 7.9 2区 医学
Immunity & Ageing Pub Date : 2024-05-17 DOI: 10.1186/s12979-024-00435-2
Tovia Jacobs, Sean R Jacobson, Juan Fortea, Jeffrey S Berger, Alok Vedvyas, Karyn Marsh, Tianshe He, Eugenio Gutierrez-Jimenez, Nathanael R Fillmore, Moses Gonzalez, Luisa Figueredo, Naomi L Gaggi, Chelsea Reichert Plaska, Nunzio Pomara, Esther Blessing, Rebecca Betensky, Henry Rusinek, Henrik Zetterberg, Kaj Blennow, Lidia Glodzik, Thomas M Wisniweski, Mony J de Leon, Ricardo S Osorio, Jaime Ramos-Cejudo
{"title":"The neutrophil to lymphocyte ratio associates with markers of Alzheimer's disease pathology in cognitively unimpaired elderly people.","authors":"Tovia Jacobs, Sean R Jacobson, Juan Fortea, Jeffrey S Berger, Alok Vedvyas, Karyn Marsh, Tianshe He, Eugenio Gutierrez-Jimenez, Nathanael R Fillmore, Moses Gonzalez, Luisa Figueredo, Naomi L Gaggi, Chelsea Reichert Plaska, Nunzio Pomara, Esther Blessing, Rebecca Betensky, Henry Rusinek, Henrik Zetterberg, Kaj Blennow, Lidia Glodzik, Thomas M Wisniweski, Mony J de Leon, Ricardo S Osorio, Jaime Ramos-Cejudo","doi":"10.1186/s12979-024-00435-2","DOIUrl":"10.1186/s12979-024-00435-2","url":null,"abstract":"<p><strong>Background: </strong>An elevated neutrophil-lymphocyte ratio (NLR) in blood has been associated with Alzheimer's disease (AD). However, an elevated NLR has also been implicated in many other conditions that are risk factors for AD, prompting investigation into whether the NLR is directly linked with AD pathology or a result of underlying comorbidities. Herein, we explored the relationship between the NLR and AD biomarkers in the cerebrospinal fluid (CSF) of cognitively unimpaired (CU) subjects. Adjusting for sociodemographics, APOE4, and common comorbidities, we investigated these associations in two cohorts: the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the M.J. de Leon CSF repository at NYU. Specifically, we examined associations between the NLR and cross-sectional measures of amyloid-β42 (Aβ42), total tau (t-tau), and phosphorylated tau<sub>181</sub> (p-tau), as well as the trajectories of these CSF measures obtained longitudinally.</p><p><strong>Results: </strong>A total of 111 ADNI and 190 NYU participants classified as CU with available NLR, CSF, and covariate data were included. Compared to NYU, ADNI participants were older (73.79 vs. 61.53, p < 0.001), had a higher proportion of males (49.5% vs. 36.8%, p = 0.042), higher BMIs (27.94 vs. 25.79, p < 0.001), higher prevalence of hypertensive history (47.7% vs. 16.3%, p < 0.001), and a greater percentage of Aβ-positivity (34.2% vs. 20.0%, p = 0.009). In the ADNI cohort, we found cross-sectional associations between the NLR and CSF Aβ42 (β = -12.193, p = 0.021), but not t-tau or p-tau. In the NYU cohort, we found cross-sectional associations between the NLR and CSF t-tau (β = 26.812, p = 0.019) and p-tau (β = 3.441, p = 0.015), but not Aβ42. In the NYU cohort alone, subjects classified as Aβ + (n = 38) displayed a stronger association between the NLR and t-tau (β = 100.476, p = 0.037) compared to Aβ- subjects or the non-stratified cohort. In both cohorts, the same associations observed in the cross-sectional analyses were observed after incorporating longitudinal CSF data.</p><p><strong>Conclusions: </strong>We report associations between the NLR and Aβ42 in the older ADNI cohort, and between the NLR and t-tau and p-tau in the younger NYU cohort. Associations persisted after adjusting for comorbidities, suggesting a direct link between the NLR and AD. However, changes in associations between the NLR and specific AD biomarkers may occur as part of immunosenescence.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":null,"pages":null},"PeriodicalIF":7.9,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11100119/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140960200","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
Correction: The interplay between obesity, immunosenescence, and insulin resistance. 更正:肥胖、免疫衰老和胰岛素抵抗之间的相互作用。
IF 7.9 2区 医学
Immunity & Ageing Pub Date : 2024-05-15 DOI: 10.1186/s12979-024-00438-z
Ghazaleh Shimi, Mohammad Hassan Sohouli, Arman Ghorbani, Azam Shakery, Hamid Zand
{"title":"Correction: The interplay between obesity, immunosenescence, and insulin resistance.","authors":"Ghazaleh Shimi, Mohammad Hassan Sohouli, Arman Ghorbani, Azam Shakery, Hamid Zand","doi":"10.1186/s12979-024-00438-z","DOIUrl":"10.1186/s12979-024-00438-z","url":null,"abstract":"","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":null,"pages":null},"PeriodicalIF":7.9,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11094928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140945978","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
Irisin inhibits microglial senescence via TFAM-mediated mitochondrial metabolism in a mouse model of tauopathy. 鸢尾素通过TFAM介导的线粒体新陈代谢抑制小鼠脑干胶质细胞衰老。
IF 7.9 2区 医学
Immunity & Ageing Pub Date : 2024-05-14 DOI: 10.1186/s12979-024-00437-0
Cailin Wang, Xiufeng Wang, Shangqi Sun, Yanmin Chang, Piaopiao Lian, Hongxiu Guo, Siyi Zheng, Rong Ma, Gang Li
{"title":"Irisin inhibits microglial senescence via TFAM-mediated mitochondrial metabolism in a mouse model of tauopathy.","authors":"Cailin Wang, Xiufeng Wang, Shangqi Sun, Yanmin Chang, Piaopiao Lian, Hongxiu Guo, Siyi Zheng, Rong Ma, Gang Li","doi":"10.1186/s12979-024-00437-0","DOIUrl":"10.1186/s12979-024-00437-0","url":null,"abstract":"<p><strong>Background: </strong>The accumulation of senescent microglia has been highlighted as a critical contributor to the progression of tauopathies. Irisin, a muscle-derived hormone produced by the proteolytic cleavage of Fibronectin-domain III containing 5 (FNDC5), mediates the pleiotropic effects of exercise on the physical body. Herein, we investigate the potential role of irisin in microglial senescence in tauopathies.</p><p><strong>Methods: </strong>To model tauopathies both in vivo and in vitro, we utilized P301S tau transgenic mice and tau K18 fibril-treated microglia BV2 cells, respectively. We first examined the expression of the irisin expression and senescence phenotypes of microglia in tauopathies. Subsequently, we investigated the impact of irisin on microglial senescence and its underlying molecular mechanisms.</p><p><strong>Result: </strong>We observed a reduction in irisin levels and an onset of premature microglial senescence both in vivo and in vitro. Irisin administration was found to counteract microglial senescence and ameliorate cognitive decline in P301S mice. Mechanistically, irisin effectively inhibited microglial senescence by stimulating the expression of mitochondrial transcription factor A (TFAM), a master regulator of mitochondrial respiratory chain biogenesis, thereby enhancing mitochondrial oxidative phosphorylation (OXPHOS). Silencing TFAM eliminated the inhibitory effect of irisin on microglial senescence as well as the restorative effect of irisin on mitochondrial OXPHOS. Furthermore, the SIRT1/PGC1α signaling pathway appeared to be implicated in irisin-mediated upregulation of TFAM.</p><p><strong>Conclusion: </strong>Taken together, our study revealed that irisin mitigated microglial senescence via TFAM-driven mitochondrial biogenesis, suggesting a promising new avenue for therapeutic strategies targeting tauopathies.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":null,"pages":null},"PeriodicalIF":7.9,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11092051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140923690","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
Quercetin promotes the proportion and maturation of NK cells by binding to MYH9 and improves cognitive functions in aged mice. 槲皮素通过与 MYH9 结合促进 NK 细胞的比例和成熟,并改善老年小鼠的认知功能。
IF 7.9 2区 医学
Immunity & Ageing Pub Date : 2024-05-10 DOI: 10.1186/s12979-024-00436-1
Tingting Su, Haitao Shen, Mengyuan He, Shanshan Yang, Xue Gong, Ce Huang, Liuling Guo, Hao Wang, Shengyu Feng, Taotao Mi, Meili Zhao, Qing Liu, Fengjiao Huo, Jian-Kang Zhu, Jianbo Zhu, Hongbin Li, Hailiang Liu
{"title":"Quercetin promotes the proportion and maturation of NK cells by binding to MYH9 and improves cognitive functions in aged mice.","authors":"Tingting Su, Haitao Shen, Mengyuan He, Shanshan Yang, Xue Gong, Ce Huang, Liuling Guo, Hao Wang, Shengyu Feng, Taotao Mi, Meili Zhao, Qing Liu, Fengjiao Huo, Jian-Kang Zhu, Jianbo Zhu, Hongbin Li, Hailiang Liu","doi":"10.1186/s12979-024-00436-1","DOIUrl":"10.1186/s12979-024-00436-1","url":null,"abstract":"<p><strong>Background: </strong>Quercetin is a flavonol compound widely distributed in plants that possesses diverse biological properties, including antioxidative, anti-inflammatory, anticancer, neuroprotective and senescent cell-clearing activities. It has been shown to effectively alleviate neurodegenerative diseases and enhance cognitive functions in various models. The immune system has been implicated in the regulation of brain function and cognitive abilities. However, it remains unclear whether quercetin enhances cognitive functions by interacting with the immune system.</p><p><strong>Results: </strong>In this study, middle-aged female mice were administered quercetin via tail vein injection. Quercetin increased the proportion of NK cells, without affecting T or B cells, and improved cognitive performance. Depletion of NK cells significantly reduces cognitive ability in mice. RNA-seq analysis revealed that quercetin modulated the RNA profile of hippocampal tissues in aging animals towards a more youthful state. In vitro, quercetin significantly inhibited the differentiation of Lin<sup>-</sup>CD117<sup>+</sup> hematopoietic stem cells into NK cells. Furthermore, quercetin promoted the proportion and maturation of NK cells by binding to the MYH9 protein.</p><p><strong>Conclusions: </strong>In summary, our findings suggest that quercetin promotes the proportion and maturation of NK cells by binding to the MYH9 protein, thereby improving cognitive performance in middle-aged mice.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":null,"pages":null},"PeriodicalIF":7.9,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11084035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140905144","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
Increased levels of GM-CSF and CXCL10 and low CD8+ memory stem T Cell count are markers of immunosenescence and severe COVID-19 in older people. GM-CSF 和 CXCL10 水平的升高以及 CD8+ 记忆干 T 细胞数量的减少是老年人免疫衰老和严重 COVID-19 的标志。
IF 7.9 2区 医学
Immunity & Ageing Pub Date : 2024-05-07 DOI: 10.1186/s12979-024-00430-7
Johanne Poisson, Carine El-Sissy, Arnaud Serret-Larmande, Nikaïa Smith, Morgane Lebraud, Jean-Loup Augy, Catherine Conti, Cécile Gonnin, Benjamin Planquette, Jean-Benoît Arlet, Bertrand Hermann, Bruno Charbit, Jean Pastre, Floriane Devaux, Cyrielle Ladavière, Lydie Lim, Pauline Ober, Johanna Cannovas, Lucie Biard, Marie-Christelle Gulczynski, Noémie Blumenthal, Hélène Péré, Camille Knosp, Alain Gey, Nadine Benhamouda, Juliette Murris, David Veyer, Eric Tartour, Jean-Luc Diehl, Darragh Duffy, Elena Paillaud, Clémence Granier
{"title":"Increased levels of GM-CSF and CXCL10 and low CD8<sup>+</sup> memory stem T Cell count are markers of immunosenescence and severe COVID-19 in older people.","authors":"Johanne Poisson, Carine El-Sissy, Arnaud Serret-Larmande, Nikaïa Smith, Morgane Lebraud, Jean-Loup Augy, Catherine Conti, Cécile Gonnin, Benjamin Planquette, Jean-Benoît Arlet, Bertrand Hermann, Bruno Charbit, Jean Pastre, Floriane Devaux, Cyrielle Ladavière, Lydie Lim, Pauline Ober, Johanna Cannovas, Lucie Biard, Marie-Christelle Gulczynski, Noémie Blumenthal, Hélène Péré, Camille Knosp, Alain Gey, Nadine Benhamouda, Juliette Murris, David Veyer, Eric Tartour, Jean-Luc Diehl, Darragh Duffy, Elena Paillaud, Clémence Granier","doi":"10.1186/s12979-024-00430-7","DOIUrl":"10.1186/s12979-024-00430-7","url":null,"abstract":"<p><strong>Background: </strong>Ageing leads to altered immune responses, resulting in higher susceptibility to certain infections in the elderly. Immune ageing is a heterogeneous process also associated with inflammaging, a low-grade chronic inflammation. Altered cytotoxic T cell responses and cytokine storm have previously been described in severe COVID-19 cases, however the parameters responsible for such immune response failures are not well known. The aim of our study was to characterize CD8<sup>+</sup> T cells and cytokines associated with ageing, in a cohort of patients aged over 70 years stratified by COVID-19 severity.</p><p><strong>Results: </strong>One hundred and four patients were included in the study. We found that, in older people, COVID-19 severity was associated with (i) higher level of GM-CSF, CXCL10 (IP-10), VEGF, IL-1β, CCL2 (MCP-1) and the neutrophil to lymphocyte ratio (NLR), (ii) increased terminally differentiated CD8<sup>+</sup>T cells, and (ii) decreased early precursors CD8<sup>+</sup> T stem cell-like memory cells (TSCM) and CD27<sup>+</sup>CD28<sup>+</sup>. The cytokines mentioned above were found at higher concentrations in the COVID-19<sup>+</sup> older cohort compared to a younger cohort in which they were not associated with disease severity.</p><p><strong>Conclusions: </strong>Our results highlight the particular importance of the myeloid lineage in COVID-19 severity among older people. As GM-CSF and CXCL10 were not associated with COVID-19 severity in younger patients, they may represent disease severity specific markers of ageing and should be considered in older people care.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":null,"pages":null},"PeriodicalIF":7.9,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11075216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140877910","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
Sexual dimorphism in atherosclerotic plaques of aged Ldlr−/− mice 老年 Ldlr-/- 小鼠动脉粥样硬化斑块的性别双态性
IF 7.9 2区 医学
Immunity & Ageing Pub Date : 2024-05-02 DOI: 10.1186/s12979-024-00434-3
Virginia Smit, Jill de Mol, Mireia N. A. Bernabé Kleijn, Marie A. C. Depuydt, Menno P. J. de Winther, Ilze Bot, Johan Kuiper, Amanda C. Foks
{"title":"Sexual dimorphism in atherosclerotic plaques of aged Ldlr−/− mice","authors":"Virginia Smit, Jill de Mol, Mireia N. A. Bernabé Kleijn, Marie A. C. Depuydt, Menno P. J. de Winther, Ilze Bot, Johan Kuiper, Amanda C. Foks","doi":"10.1186/s12979-024-00434-3","DOIUrl":"https://doi.org/10.1186/s12979-024-00434-3","url":null,"abstract":"Atherosclerosis, the main underlying pathology of cardiovascular disease, is a chronic inflammatory disease characterized by lipid accumulation and immune cell responses in the vascular wall, resulting in plaque formation. It is well-known that atherosclerosis prevalence and manifestation vary by sex. However, sexual dimorphism in the immune landscape of atherosclerotic plaques has up to date not been studied at high-resolution. In this study, we investigated sex-specific differences in atherosclerosis development and the immunological landscape of aortas at single-cell level in aged Ldlr−/− mice. We compared plaque morphology between aged male and female chow diet-fed Ldlr−/− mice (22 months old) with histological analysis. Using single-cell RNA-sequencing and flow cytometry on CD45+ immune cells from aortas of aged Ldlr−/− mice, we explored the immune landscape in the atherosclerotic environment in males and females. We show that plaque volume is comparable in aged male and female mice, and that plaques in aged female mice contain more collagen and cholesterol crystals, but less necrotic core and macrophage content compared to males. We reveal increased immune cell infiltration in female aortas and found that expression of pro-atherogenic markers and inflammatory signaling pathways was enriched in plaque immune cells of female mice. Particularly, female aortas show enhanced activation of B cells (Egr1, Cd83, Cd180), including age-associated B cells, in addition to an increased M1/M2 macrophage ratio, where Il1b+ M1-like macrophages display a more pro-inflammatory phenotype (Nlrp3, Cxcl2, Mmp9) compared to males. In contrast, increased numbers of age-associated Gzmk+CD8+ T cells, dendritic cells, and Trem2+ macrophages were observed in male aortas. Altogether, our findings highlight that sex is a variable that contributes to immunological differences in the atherosclerotic plaque environment in mice and provide valuable insights for further preclinical studies into the impact of sex on the pathophysiology of atherosclerosis.","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":null,"pages":null},"PeriodicalIF":7.9,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140833875","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 T cell aging on the change of human tissue structure T 细胞老化对人体组织结构变化的影响
IF 7.9 2区 医学
Immunity & Ageing Pub Date : 2024-04-30 DOI: 10.1186/s12979-024-00433-4
Ling-ling Xu, Xiang Chen, Jing-ping Cheng
{"title":"The effect of T cell aging on the change of human tissue structure","authors":"Ling-ling Xu, Xiang Chen, Jing-ping Cheng","doi":"10.1186/s12979-024-00433-4","DOIUrl":"https://doi.org/10.1186/s12979-024-00433-4","url":null,"abstract":"The trend of aging of the global population is becoming more and more significant, and the incidence of age-related diseases continues to rise.This phenomenon makes the problem of aging gradually attracted wide attention of the society, and gradually developed into an independent research field.As a vital defense mechanism of the human body, the immune system changes significantly during the aging process.Age-induced changes in the body’s immune system are considered harmful and are commonly referred to as immune aging, which may represent the beginning of systemic aging.Immune cells, especially T cells, are the biggest influencers and participants in age-related deterioration of immune function, making older people more susceptible to different age-related diseases.More and more evidence shows that T cells play an important role in the change of human tissue structure after aging, which fundamentally affects the health and survival of the elderly.In this review, we discuss the general characteristics of age-related T cell immune alterations and the possible effects of aging T cells in various tissue structures in the human body.","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":null,"pages":null},"PeriodicalIF":7.9,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140833879","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
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