Immunity & Ageing最新文献

{"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":"21 1","pages":"31"},"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}

{"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":"21 1","pages":"30"},"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}

{"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^-CD117⁺ 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":"21 1","pages":"29"},"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}

{"title":"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.","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⁺ 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⁺T cells, and (ii) decreased early precursors CD8⁺ T stem cell-like memory cells (TSCM) and CD27⁺CD28⁺. The cytokines mentioned above were found at higher concentrations in the COVID-19⁺ 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":"21 1","pages":"28"},"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}

{"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":"37 1","pages":""},"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}

{"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":"97 1","pages":""},"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}

{"title":"Correction: The impact of ageing on the distribution of preformed anti-HLA and anti-MICA antibody specificities in recipients from eastern China prior to initial HSCT","authors":"Qinqin Pan, Xiao Ma, Yajie You, Yuejiao Yu, Su Fan, Xiaoyan Wang, Mengyuan Wang, Ming Gao, Guangming Gong, Kourong Miao, Jie Shen, Xiaoyu Zhou","doi":"10.1186/s12979-024-00428-1","DOIUrl":"https://doi.org/10.1186/s12979-024-00428-1","url":null,"abstract":"&lt;p&gt;&lt;b&gt;Correction: Immun Ageing 21, 15 (2024)&lt;/b&gt;.&lt;/p&gt;&lt;p&gt;&lt;b&gt;https://doi.org/10.1186/s12979-024-00417-4&lt;/b&gt;&lt;/p&gt;&lt;p&gt;Following publication of the original article [1], the Editors-in-Chief of &lt;i&gt;Immunity &amp; Ageing&lt;/i&gt; requested to update the article title with the approval of the authors from “Ageing on the impact of distribution about preformed anti‑HLA and anti‑MICA antibody specificities in recipients prior to initial HSCT from East China” to “The impact of ageing on the distribution of preformed anti-HLA and anti-MICA antibody specificities in recipients from eastern China prior to initial HSCT’.&lt;/p&gt;&lt;p&gt;The original article [1] has been updated.&lt;/p&gt;&lt;ol data-track-component=\"outbound reference\"&gt;&lt;li data-counter=\"1.\"&gt;&lt;p&gt;Pan Q, Ma X, You Y et al. The impact of ageing on the distribution of preformed anti-HLA and anti-MICA antibody specificities in recipients from eastern China prior to initial HSCT. Immun Ageing 21, 15 (2024). https://doi.org/10.1186/s12979-024-00417-4.&lt;/p&gt;&lt;/li&gt;&lt;/ol&gt;&lt;p&gt;Download references&lt;svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"&gt;&lt;use xlink:href=\"#icon-eds-i-download-medium\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"&gt;&lt;/use&gt;&lt;/svg&gt;&lt;/p&gt;&lt;h3&gt;Authors and Affiliations&lt;/h3&gt;&lt;ol&gt;&lt;li&gt;&lt;p&gt;HLA Lab, Department of Transfusion, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, 210029, China&lt;/p&gt;&lt;p&gt;Qinqin Pan, Xiao Ma, Yajie You, Yuejiao Yu, Su Fan, Xiaoyan Wang, Mengyuan Wang, Jie Shen &amp; Xiaoyu Zhou&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;p&gt;Department of Pharmacy, Jinling Hospital, Nanjing University School of Medicine, Nanjing, 210002, China&lt;/p&gt;&lt;p&gt;Ming Gao &amp; Guangming Gong&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;p&gt;Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, 210029, China&lt;/p&gt;&lt;p&gt;Kourong Miao&lt;/p&gt;&lt;/li&gt;&lt;/ol&gt;&lt;span&gt;Authors&lt;/span&gt;&lt;ol&gt;&lt;li&gt;&lt;span&gt;Qinqin Pan&lt;/span&gt;View author publications&lt;p&gt;You can also search for this author in &lt;span&gt;PubMed&lt;span&gt; &lt;/span&gt;Google Scholar&lt;/span&gt;&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;Xiao Ma&lt;/span&gt;View author publications&lt;p&gt;You can also search for this author in &lt;span&gt;PubMed&lt;span&gt; &lt;/span&gt;Google Scholar&lt;/span&gt;&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;Yajie You&lt;/span&gt;View author publications&lt;p&gt;You can also search for this author in &lt;span&gt;PubMed&lt;span&gt; &lt;/span&gt;Google Scholar&lt;/span&gt;&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;Yuejiao Yu&lt;/span&gt;View author publications&lt;p&gt;You can also search for this author in &lt;span&gt;PubMed&lt;span&gt; &lt;/span&gt;Google Scholar&lt;/span&gt;&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;Su Fan&lt;/span&gt;View author publications&lt;p&gt;You can also search for this author in &lt;span&gt;PubMed&lt;span&gt; &lt;/span&gt;Google Scholar&lt;/span&gt;&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;Xiaoyan Wang&lt;/span&gt;View author publications&lt;p&gt;You can also search for this author in &lt;span&gt;PubMed&lt;span&gt; &lt;/span&gt;Google Scholar&lt;/span&gt;&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;Mengyuan Wang&lt;/span&gt;View author publications&lt;p&gt;You can also search for this author in &lt;span&gt;PubMed&lt;span&gt; &lt;/span&gt;Google Scholar&lt;/span&gt;&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;Ming Gao&lt;/span&gt;View author publications&lt;p&gt;You can also search for this author in &lt;s","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"39 1","pages":""},"PeriodicalIF":7.9,"publicationDate":"2024-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140567110","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}

{"title":"Role of germinal center and CD39highCD73+ B cells in the age-related tonsillar involution","authors":"Rocío Pastor, Juliana Puyssegur, M. Paula de la Guardia, Lindybeth Sarmiento Varón, Gladys Beccaglia, Nicolás Spada, Andrea Paes de Lima, M. Soledad Collado, Andrés Blanco, Isabel Aspe Scetti, M. Elena Arabolaza, Bibiana Paoli, Fernando Chirdo, Eloísa Arana","doi":"10.1186/s12979-024-00425-4","DOIUrl":"https://doi.org/10.1186/s12979-024-00425-4","url":null,"abstract":"The tonsils operate as a protection ring of mucosa at the gates of the upper aero-digestive tract. They show similarities with lymph nodes and participate as inductive organs of systemic and mucosal immunity. Based on the reduction of their size since puberty, they are thought to experience involution in adulthood. In this context, we have used tonsillar mononuclear cells (TMC) isolated from patients at different stages of life, to study the effect of ageing and the concomitant persistent inflammation on these immune cells. We found an age-dependent reduction in the proportion of germinal center B cell population (BGC) and its T cell counterpart (T follicular helper germinal center cells, TfhGC). Also, we demonstrated an increment in the percentage of local memory B cells and mantle zone T follicular helper cells (mTfh). Furthermore, younger tonsils rendered higher proportion of proliferative immune cells within the freshly isolated TMC fraction than those from older ones. We demonstrated the accumulation of a B cell subset (CD20+CD39highCD73+ cells) metabolically adapted to catabolize adenosine triphosphate (ATP) as patients get older. To finish, tonsillar B cells from patients at different ages did not show differences in their proliferative response to stimulation ex vivo, in bulk TMC cultures. This paper sheds light on the changing aspects of the immune cellular landscape, over the course of time and constant exposure, at the entrance of the respiratory and digestive systems. Our findings support the notion that there is a re-modelling of the immune functionality of the excised tonsils over time. They are indicative of a transition from an effector type of immune response, typically oriented to reduce pathogen burden early in life, to the development of an immunosuppressive microenvironment at later stages, when tissue damage control gets critical provided the time passed under immune attack. Noteworthy, when isolated from such histologic microenvironment, older tonsillar B cells seem to level their proliferation capacity with the younger ones. Understanding these features will not only contribute to comprehend the differences in susceptibility to pathogens among children and adults but would also impact on vaccine developments intended to target these relevant mucosal sites.","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"2 1","pages":""},"PeriodicalIF":7.9,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140566815","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}

{"title":"Addition of inflammation-related biomarkers to the CAIDE model for risk prediction of all-cause dementia, Alzheimer’s disease and vascular dementia in a prospective study","authors":"Kira Trares, Manuel Wiesenfarth, Hannah Stocker, Laura Perna, Agnese Petrera, Stefanie M. Hauck, Konrad Beyreuther, Hermann Brenner, Ben Schöttker","doi":"10.1186/s12979-024-00427-2","DOIUrl":"https://doi.org/10.1186/s12979-024-00427-2","url":null,"abstract":"It is of interest whether inflammatory biomarkers can improve dementia prediction models, such as the widely used Cardiovascular Risk Factors, Aging and Dementia (CAIDE) model. The Olink Target 96 Inflammation panel was assessed in a nested case-cohort design within a large, population-based German cohort study (n = 9940; age-range: 50–75 years). All study participants who developed dementia over 20 years of follow-up and had complete CAIDE variable data (n = 562, including 173 Alzheimer’s disease (AD) and 199 vascular dementia (VD) cases) as well as n = 1,356 controls were selected for measurements. 69 inflammation-related biomarkers were eligible for use. LASSO logistic regression and bootstrapping were utilized to select relevant biomarkers and determine areas under the curve (AUCs). The CAIDE model 2 (including Apolipoprotein E (APOE) ε4 carrier status) predicted all-cause dementia, AD, and VD better than CAIDE model 1 (without APOE ε4) with AUCs of 0.725, 0.752 and 0.707, respectively. Although 20, 7, and 4 inflammation-related biomarkers were selected by LASSO regression to improve CAIDE model 2, the AUCs did not increase markedly. CAIDE models 1 and 2 generally performed better in mid-life (50–64 years) than in late-life (65–75 years) sub-samples of our cohort, but again, inflammation-related biomarkers did not improve their predictive abilities. Despite a lack of improvement in dementia risk prediction, the selected inflammation-related biomarkers were significantly associated with dementia outcomes and may serve as a starting point to further elucidate the pathogenesis of dementia.","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"25 1","pages":""},"PeriodicalIF":7.9,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140566814","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}

{"title":"B-1 derived anti-Thy-1 B cells in old aged mice develop lymphoma/leukemia with high expression of CD11b and Hamp2 that different from TCL1 transgenic mice","authors":"Kyoko Hayakawa, Yan Zhou, Susan A. Shinton","doi":"10.1186/s12979-024-00415-6","DOIUrl":"https://doi.org/10.1186/s12979-024-00415-6","url":null,"abstract":"Human old aged unmutated chronic lymphocytic leukemia U-CLL are the TCL1+ZAP70+CD5+ B cells. Since CD5 makes the BCR signaling tolerance, ZAP70 increased in U-CLL not only TCL1+ alone. In mice, TCL1 (TCL1A) is the negative from neonate to old aged, as TC–. VH8-12/Vk21-5 is the anti-thymocyte/Thy-1 autoreactive ATA B cell. When ATA μκTg generation in mice, ATA B cells are the neonate generated CD5+ B cells in B-1, and in the middle age, CD5+ can be down or continuously CD5+, then, old aged CLL/lymphoma generation with increased CD11b in TC–ZAP70–CD5– or TC–ZAP70+CD5+. In this old aged TC–ATA B microarray analysis showed most similar to human CLL and U-CLL, and TC–ZAP70+CD5+ showed certain higher present as U-CLL. Original neonate ATA B cells showed with several genes down or further increase in old aged tumor, and old aged T-bet+CD11c+, CTNNB1hi, HMGBhi, CXCR4hi, DPP4hi and decreased miR181b. These old aged increased genes and down miR181b are similar to human CLL. Also, in old age ATA B cell tumor, high CD38++CD44++, increased Ki67+ AID+, and decreased CD180– miR15Olow are similar to U-CLL. In this old aged ATA B, increased TLR7,9 and Wnt10b. TC+Tg generated with ATAμκTg mice occurred middle age tumor as TC+ZAP70–CD5+ or TC+ZAP70+CD5+, with high NF-kB1, TLR4,6 and Wnt5b,6 without increased CD11b. Since neonatal state to age with TC+Tg continuously, middle age CLL/lymphoma generation is not similar to old aged generated, however, some increased in TC+ZAP70+ are similar to the old age TC– ATA B tumor. Then, TC– ATA B old age tumor showed some difference to human CLL. ATA B cells showed CD11b+CD22++, CD24 down, and hepcidin Hamp2++ with iron down. This mouse V8-12 similar to human V2-5, and V2-5 showed several cancers with macrophages/neutrophils generated hepcidin+ ironlow or some showed hepcidin– iron+ with tumor, and mouse V8-12 with different Vk19-17 generate MZ B cells strongly increased macrophage++ in old aged and generated intestine/colon tumor. Conclusion, neonate generated TC–ATA B1 cells in old aged tumor generation are CD11b+ in the leukemia CLL together with lymphoma cancer with hepcidin-related Hamp2++ in B-1 cell generation to control iron.","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"87 1","pages":""},"PeriodicalIF":7.9,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140567112","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}