Journal of cellular immunology最新文献

{"title":"Glucose Metabolism is a Better Marker for Predicting Clinical Alzheimer’s Disease than Amyloid or Tau","authors":"Tyler C. Hammond, Ai-Ling Lin","doi":"10.33696/immunology.4.128","DOIUrl":"https://doi.org/10.33696/immunology.4.128","url":null,"abstract":"Alzheimer’s disease (AD) research has long been dominated with communications regarding the amyloid hypothesis and targeting amyloid clearance through pharmacological therapies from the brain [1]. Unfortunately, this research strategy has yielded only one new FDA-accelerated approved therapeutic for early AD, and its clinical benefit still needs to be verified [2]. It may be time to employ a new strategy in AD therapeutics research. Hammond et al. reported that diminished uptake of glucose in the brain is a better marker for classifying AD than beta-amyloid (A β ) or phosphorylated tau deposition [3]. The National Institute on Aging and the Alzheimer’s Association published revised guidelines for the diagnosis of AD to include the measurement of amyloid (A), tau (T), and neurodegeneration (N), when diagnosing and treating AD [4]. It is highly relevant to AD therapeutic research whether amyloid, tau, and neurodegeneration contribute equally to the progression of AD at all phases of the disease or in a matter dependent on disease phase. To be able to successfully treat or prevent AD, there is a pressing need to identify precision biomarkers that are sensitive to disease progression and able to predict onset of cognitive impairment [5]. Hammond et al. used an advanced statistical learning machine learning method, random forest, on data provided by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) to measure the ability of beta-amyloid measured by positron emission tomography (A β -PET), phosphorylated tau measured in the cerebral spinal fluid (CSF-pTau), fluorodeoxyglucose measured by positron emission tomography (FDG-PET) and structural imaging measured by magnetic resonance imaging (MRI) to classify AD diagnosis. Their results demonstrated that amyloid, tau, and neurodegeneration have a phase-dependent impact on the development of AD. A β and pTau are better predictors of the early dementia status that is often defined as mild cognitive impairment (MCI), and neurodegeneration, especially low glucose uptake, is a better predictor of later dementia status, or clinical AD. A","PeriodicalId":73644,"journal":{"name":"Journal of cellular immunology","volume":"4 1","pages":"15 - 18"},"PeriodicalIF":0.0,"publicationDate":"2022-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42196487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glucose Metabolism is a Better Marker for Predicting Clinical Alzheimer's Disease than Amyloid or Tau.","authors":"Tyler C Hammond, Ai-Ling Lin","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":73644,"journal":{"name":"Journal of cellular immunology","volume":"4 1","pages":"15-18"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8975178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9704016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PD-L1 as a Novel Mediator of Lung Fibroblast to Myofibroblast Transition.","authors":"Xia Guo, Guoqing Qian","doi":"10.33696/immunology.4.142","DOIUrl":"https://doi.org/10.33696/immunology.4.142","url":null,"abstract":"of levels of high PD-L1","PeriodicalId":73644,"journal":{"name":"Journal of cellular immunology","volume":"4 4","pages":"141-144"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9696593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40512816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of Gene Editing versus a Neutrophil Elastase Inhibitor as Potential Therapies for <i>ELANE</i> Neutropenia.","authors":"Vahagn Makaryan,&nbsp;Merideth Kelley,&nbsp;Breanna Fletcher,&nbsp;Isabella Archibald,&nbsp;Tanoya Poulsen,&nbsp;David Dale","doi":"10.33696/immunology.4.129","DOIUrl":"https://doi.org/10.33696/immunology.4.129","url":null,"abstract":"<p><p>Heterozygous mutations in <i>ELANE</i>, the gene for neutrophil elastase, cause cyclic and congenital neutropenia through the programed cell death of neutrophil progenitors in the bone marrow. Granulocyte colony-stimulating factor is an effective therapy for these diseases, but alternative therapies are needed, especially for patients who do not respond well or are at high risk of developing myeloid malignancies. We developed an HL60 cell model for <i>ELANE</i> neutropenia and previously demonstrated that transient and regulated expression of mutant <i>ELANE</i> causes cell death by accelerated apoptosis. Knocking down the mutant gene or exposure to a potent inhibitor of neutrophil elastase rescued neutrophil development. Because of the great diversity in causative <i>ELANE</i> mutations, we generated stable HL60 clones expressing mutant P139L, C151Y and G214R and compared the effects of elastase inhibitor exposure to an <i>ELANE</i> knock-out line on cell development and function. ATRA induced differentiation demonstrated comparably impaired myeloid cell development for all three lines with upregulated expression of GRP78/BIP, an abnormality corrected by exposure of these cells to the elastase inhibitor MK-0339. The inhibitor and KO of mutant <i>ELANE</i> led to formation of neutrophils with comparable chemotactic and bactericidal capacities. We concluded that both strategies have great potential for the treatment of cyclic and congenital neutropenia. However, an orally absorbed, cell permeable inhibitor of neutrophil elastase, if proven safe and effective in a clinical trial, might be the better alternative to G-CSF or gene editing to treat <i>ELANE</i> neutropenia.</p>","PeriodicalId":73644,"journal":{"name":"Journal of cellular immunology","volume":" ","pages":"19-28"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9431957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40342901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Commentary: Experimental Mouse Models of Invasive Candidiasis Caused by <i>Candida auris</i> and Other Medically Important <i>Candida</i> Species.","authors":"Hong Xin","doi":"10.33696/immunology.4.130","DOIUrl":"https://doi.org/10.33696/immunology.4.130","url":null,"abstract":"<p><p>The study \"<b>\"Experimental Mouse Models of Disseminated <i>Candida auris</i> Infection\"</b> provides the first insight into the critical role of C5 in the host antimicrobial defense to <i>disseminated candidiasis caused by C. auris</i>. This study also establishes an inbred A/J mouse model of systemic <i>C. auris</i> infection without drug-induced immunosuppression. <i>C. auris</i> has become the first fungal pathogen causing global public health threat due to its multidrug resistance (MDR) and persistence in hospital and nursing home settings. Currently, as compared to <i>C. albicans</i>, very limited animal models are available to study the progression of non<i>-albicans Candida</i> (NAC) species including <i>C. auris</i>. We have successfully established immunosuppressed C57BL/6, BALB/c and A/J murine models of disseminated candidiasis caused by five clinically significant <i>Candida</i> species: <i>C</i>. <i>albicans, C. glabrata, C. tropicalis, C. parapsilosis</i> and <i>C. auris</i>. Here we also report updated progress of some important mouse models for <i>C. auris</i> infection in the field. These valuable mouse models can be used for the assessment of antifungal drugs, evaluation of potential vaccines and monoclonal antibodies (mAbs) to protect before and after candidiasis, and comparison of pathogenicity of different <i>Candida</i> species.</p>","PeriodicalId":73644,"journal":{"name":"Journal of cellular immunology","volume":" ","pages":"29-33"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9286494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40624911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Issue of Monocyte Activation in ASD: Troubles with Translation.","authors":"R J Moreno,&nbsp;P Ashwood","doi":"10.33696/immunology.4.146","DOIUrl":"https://doi.org/10.33696/immunology.4.146","url":null,"abstract":"<p><p>Autism spectrum disorder (ASD) prevalence has increased year on year for the past two decades and currently affects 1 in 44 individuals in the US. An increasing number of studies have pointed to increased immune activation as both an etiological agent and also involved in the ongoing pathological process of ASD. Both adaptive and innate immune responses have been implicated. Evidence of innate dysregulation has so far included increased production of innate inflammatory cytokines, increased cell numbers, and altered activation in monocytes in the blood and microglia in the brain. Suggesting an orchestrated innate immune response may be involved in ASD. Hughes et al. (2022) recently assessed transcriptome differences that could underlie altered activation of monocytes using next-generation bulk-RNA sequencing on isolated CD14+ monocytes at baseline and after activation with different Toll-like receptor agonists. Circulating CD14+ monocyte from children with autistic disorder (AD) and children diagnosed with perverse developmental disorder not otherwise specified (PDD-NOS) were found to differ in a number of activation pathways after gene enrichment analysis compared to typically developing children. There was an overall upregulation in translational machinery in both neurodevelopmental disorder groups, whereas typically developing children were downregulated, indicating an issue with monocyte activation. Several identified differentially expressed genes in monocytes were also identified as ASD at-risk genes, according to the Simons Foundation Autism Research Initiative (SFARI), and genes involved in inflammatory bowel diseases. This work implicates altered monocyte activation with a lack of regulation as a potential mechanistic issue in ASD. Future work is warranted to evaluate how monocyte regulatory mechanisms differ in ASD individuals.</p>","PeriodicalId":73644,"journal":{"name":"Journal of cellular immunology","volume":"4 5","pages":"167-170"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9853954/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10618696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preliminary Evidence of Differentially Induced Immune Responses by Microparticle-adsorbed LPS in Patients with Crohn's Disease.","authors":"P Ashwood","doi":"10.33696/immunology.4.152","DOIUrl":"10.33696/immunology.4.152","url":null,"abstract":"<p><p>Inorganic microparticles are ubiquitous in the modern Western diet present as food additives and are actively scavenged by microfold (M) cells overlying human intestinal lymphoid aggregates. In Crohn's disease (CD), inflammation is caused by the inability of the intestinal mucosa to sustain tolerance to gut luminal factors including bacteria and their by-products. Having large, highly charged surface areas dietary particles can avidly bind biomolecules such as lipopolysaccharide (LPS). The aim of this paper was to examine whether the dietary particle, titanium dioxide (TiO₂), modified cellular immune responses to LPS differently in peripheral blood mononuclear cells (PBMC) from CD patients compared with healthy controls. Our data showed that LPS-associated particles predominantly stimulated release of IL-1β and induced concurrent cell death in peripheral monocytes following particle uptake in both health and disease. In addition, IL-1β release was increased more in CD patients compared with controls following particle stimulation. In conclusion, LPS adsorption to dietary particulates provides a mechanism for stimulation of phagocytic mononuclear cells and may cause aggravation of mucosal immune responses in inflammatory conditions of the bowel such as CD, irritable bowel syndrome, and autism spectrum disorder and schizophrenia associated gastrointestinal conditions, by immune priming mediated through increased production of pro-inflammatory cytokines.</p>","PeriodicalId":73644,"journal":{"name":"Journal of cellular immunology","volume":"4 6","pages":"211-218"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9977324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9077777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolution of the RNA Cleavage Subunit C11/RPC10, and Recycling by RNA Polymerase III.","authors":"Saurabh Mishra, Richard J Maraia","doi":"10.33696/immunology.4.133","DOIUrl":"10.33696/immunology.4.133","url":null,"abstract":"<p><p>Nuclear RNA polymerase (Pol) III synthesizes large amounts of tRNAs and other short non-coding (nc)RNAs by a unique process that involves a termination-associated reinitiation-recycling mechanism. In addition to its two largest of 17 subunits, which contribute to active center RNA-DNA binding and catalytic site, a smaller subunit of ~110 aa (yeast C11, human RPC10) monitors this site, can modify its activity, and is essential for reinitiation-recycling. Distinct, but relevant to human immunity is cytoplasmic (cyto-)Pol III that is a direct sensor of AT-rich viral DNA from which it synthesizes 5'-ppp-RNA signaling molecules that activate interferon (IFN) production. Mutations in genes encoding Pol III subunits cause severe anti-viral immunodeficiency although the mechanisms responsible for cyto-Pol III initiation on this AT-rich DNA are unknown. Cyto-Pol III has also been implicated in inducing IFN in response to cytosolic mitochondrial DNA in autoimmune dysfunction. A focus of this commentary is recent biochemical and genetics research that examined the roles of the individual domains of C11 in the Pol III termination-associated reinitiation-recycling process as well as more recent cryo-EM structural and accompanying analyses, that are considered in evolutionary and other biological contexts. The N-terminal domain (NTD) of C11/RPC10 anchors at the periphery of Pol III from which a highly conserved linker extends to the mobile C-terminal RNA cleavage domain that can reach into the active center and rescue arrested complexes. Biochemical data indicate separable activities for the NTD and CTD in the transcription cycle, whereas the NTD-Linker can confer the evolutionary unique Pol III termination-reinitiation-recycling activity. A model produced from single particle cryo-EM conformations indicates that the C11-Linker-CTD swings in and out of the active center coordinated with allosteric movements of the DNA-binding clamp by the largest subunit, coupling termination to reinitiation-recycling. These may be relevant to DNA loading by cyto-Pol III during immune signaling.</p>","PeriodicalId":73644,"journal":{"name":"Journal of cellular immunology","volume":" ","pages":"65-71"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9262308/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40580760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inulin Supplementation Mitigates Gut Dysbiosis and Brain Impairment Induced by Mild Traumatic Brain Injury during Chronic Phase.","authors":"Lucille M Yanckello, Brian Fanelli, Scott McCulloch, Xin Xing, McKenna Sun, Tyler C Hammond, Rita Colwell, Zezong Gu, Aaron C Ericsson, Ya-Hsuan Chang, Adam D Bachstetter, Ai-Ling Lin","doi":"10.33696/immunology.4.132","DOIUrl":"10.33696/immunology.4.132","url":null,"abstract":"<p><p>Mild traumatic brain injury (mTBI) has been shown to acutely alter the gut microbiome diversity and composition, known as dysbiosis, which can further exacerbate metabolic and vascular changes in the brain in both humans and rodents. However, it remains unknown how mTBI affects the gut microbiome in the chronic phase recovery (past one week post injury). It is also unknown if injury recovery can be improved by mitigating dysbiosis. The goal of the study is to fill the knowledge gap. First, we aim to understand how mTBI alters the gut microbiome through the chronic period of recovery (3 months post injury). In addition, as the gut microbiome can be modulated by diet, we also investigated if prebiotic inulin, a fermentable fiber that promotes growth of beneficial bacteria and metabolites, would mitigate dysbiosis, improve systemic metabolism, and protect brain structural and vascular integrity when administered after 3 months post closed head injury (CHI). We found that CHI given to male mice at 4 months of age induced gut dysbiosis which peaked at 1.5 months post injury, reduced cerebral blood flow (CBF) and altered brain white matter integrity. Interestingly, we also found that Sham mice had transient dysbiosis, which peaked 24 hours after injury and then normalized. After 8 weeks of inulin feeding, CHI mice had increased abundance of beneficial/anti-inflammatory bacteria, reduced abundance of pathogenic bacteria, enriched levels of short-chain fatty acids, and restored CBF in both hippocampi and left thalamus, compared to the CHI-control fed and Sham groups. Using machine learning, we further identified top bacterial species that separate Sham and CHI mice with and without the diet. Our results indicate that there is an injury- and time-dependent dysbiosis between CHI and Sham mice; inulin is effective to mitigate dysbiosis and improve brain injury recovery in the CHI mice. As there are currently no effective treatments for mTBI, the study may have profound implications for developing therapeutics or preventive interventions in the future.</p>","PeriodicalId":73644,"journal":{"name":"Journal of cellular immunology","volume":"4 2","pages":"50-64"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9126115/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9335050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Return of Tocilizumab for Patients with COVID-19 Pneumonia","authors":"Kathy Tin, A. Fernandes, Roderick A. Go","doi":"10.33696/immunology.3.119","DOIUrl":"https://doi.org/10.33696/immunology.3.119","url":null,"abstract":"The COVID-19 pandemic has now impacted the global population for over a year. It has been devastating for many and has challenged us all in many ways. While the advent of vaccinations looks to curtail the number of cases, multiple challenges to ending the pandemic remain, including the advent of variants, vaccine hesitancy, access to vaccines, and the impaired efficacy of vaccines in immunocompromised persons. Thus, it is still essential to continue investigating treatments for COVID-19.","PeriodicalId":73644,"journal":{"name":"Journal of cellular immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45635610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}