scholarly journals High resolution profile of body wide pathological changes induced by abnormal elastin metabolism in Loxl1 knockout mice

2018 ◽  
Author(s):  
Bingbing Wu ◽  
Yu Li ◽  
Chengrui An ◽  
Deming Jiang ◽  
Lin Gong ◽  
...  
Keyword(s):  
Immune Cell ◽  
Cell Mass ◽  
Transcriptome Profiling ◽  
Multiple Organ ◽  
Mass Cytometry ◽  
Tumor Patients ◽  
Cancer Pathology ◽  
Immune Cell Subpopulations ◽  
Cell Subpopulations ◽  
Immune Changes

AbstractAbnormal ECM caused serious body wide diseases and elastin is one of the important ECM components. But its systemic function still has not yet been thoroughly illustrated due to limitations related to novel research technologies. To uncover the functions of elastin, a new method for body-wide organ transcriptome profiling, combined with single-cell mass cytometry of the blood, was developed. A body-wide organ transcriptomic (BOT) map was created by performing RNA-seq of 17 organs from both Loxl1 knockout (KO) and wide type (WT) mice. The BOT results showed a systematic up-regulation of genes related to immune response and proliferation process in multiple tissues of the KO mice; histological and immune staining also confirmed the hyperplasia and infiltration of local immune cells in the vagina, small intestine, and liver tissues of KO mice. Furthermore, using 32 markers, CYTOF mass cytometry analysis of the immune cell subpopulations from the peripheral blood revealed apparent systemic immune changes in the KO mice; data showed an activated NK cells and T cells with a higher expression of CD44 and CD38, and a suppressed B cells, macrophages and neutrophils with lower expressions of CD62L, CD44 and IL6. More interestingly, these findings also correlated well with the data obtained from cancer patient databases; tumor patients had higher mutation frequency of Loxl1, and the Loxl1-mutant tumor patients had up-regulated immune process, cell proliferation and decreased survival rate. Thus, this research provided a powerful strategy to screen body-wide organ functions of a particular gene; the findings also illustrated the important biological roles of elastin on multiple organ cells and systemic immunity. These strategy and discoveries are both of important value for the understanding of ECM biology and multi-organ cancer pathology.

scholarly journals Single‐Cell Immune Profiling in Coronary Artery Disease: The Role of State‐of‐the‐Art Immunophenotyping With Mass Cytometry in the Diagnosis of Atherosclerosis

2020 ◽  
Vol 9 (24) ◽  
Author(s):  
Katharine A. Kott ◽  
Stephen T. Vernon ◽  
Thomas Hansen ◽  
Macha de Dreu ◽  
Souvik K. Das ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Single Cell ◽  
Immune Cell ◽  
Mass Cytometry ◽  
Artery Disease ◽  
Immune Cell Subpopulations ◽  
Cell Subpopulations ◽  
Serological Biomarkers

Abstract Coronary artery disease remains the leading cause of death globally and is a major burden to every health system in the world. There have been significant improvements in risk modification, treatments, and mortality; however, our ability to detect asymptomatic disease for early intervention remains limited. Recent discoveries regarding the inflammatory nature of atherosclerosis have prompted investigation into new methods of diagnosis and treatment of coronary artery disease. This article reviews some of the highlights of the important developments in cardioimmunology and summarizes the clinical evidence linking the immune system and atherosclerosis. It provides an overview of the major serological biomarkers that have been associated with atherosclerosis, noting the limitations of these markers attributable to low specificity, and then contrasts these serological markers with the circulating immune cell subtypes that have been found to be altered in coronary artery disease. This review then outlines the technique of mass cytometry and its ability to provide high‐dimensional single‐cell data and explores how this high‐resolution quantification of specific immune cell subpopulations may assist in the diagnosis of early atherosclerosis in combination with other complimentary techniques such as single‐cell RNA sequencing. We propose that this improved specificity has the potential to transform the detection of coronary artery disease in its early phases, facilitating targeted preventative approaches in the precision medicine era.

scholarly journals Allergic diseases influence symptom severity and T lymphocyte subgroups of children with tic disorders

2021 ◽  
pp. jim-2021-001788
Author(s):  
Xiumei Liu ◽  
Xueming Wang ◽  
Xiaoling Zhang ◽  
Ai hua Cao
Keyword(s):  
T Lymphocyte ◽  
Immune Cell ◽  
Clinical Manifestations ◽  
Allergic Diseases ◽  
Tic Disorders ◽  
Control Group ◽  
T Lymphocyte Subsets ◽  
Tic Severity ◽  
Immune Cell Subpopulations ◽  
Cell Subpopulations

Tic disorders (TD) are childhood-onset neurological disorders. Immune system dysregulation has been postulated to play a role in TD, and its mechanisms likely involve dysfunctional neural-immune cross-talk, which ultimately leads to altered maturation of the brain pathways that control different TD clinical manifestations and behavioral and emotional damages. Clinical studies have demonstrated an association between TD and allergies and overactive immune responses at a systemic level. In this study, the Yale Global Tic Severity Scale was taken as a global measure of tic severity. Compared with the control group, the group of children with TD plus allergic diseases displayed significantly increased Yale total scores (p<0.05), which suggests that children with TD plus allergic diseases have heavier tic symptoms. Both motor and vocal tic scores are higher in the group of children with TD plus allergy compared with the control group. We counted immune cell subpopulations using FACS. T lymphocyte subset comparison of CD3, CD4, CD8, and CD4:CD8 expression ratios revealed that the level of CD3, CD4, and CD4:CD8 in children with TD plus allergic diseases was significantly lower than those of children with TD without allergic diseases. These differences were statistically significant (p<0.05) and suggest that children with TD plus allergic diseases have imbalanced T lymphocyte subsets. We concluded that allergy increased the severity of TD through an imbalance in cellular immunity. Studies need to be done to show whether treatment of allergic symptoms leads to a decrease in TD manifestations.

scholarly journals Electronic Sorting of Immune Cell Subpopulations Based on Highly Plastic Genes

2016 ◽  
Vol 197 (2) ◽  
pp. 665-673 ◽  
Author(s):  
Pingzhang Wang ◽  
Wenling Han ◽  
Dalong Ma
Keyword(s):  
Immune Cell ◽  
Immune Cell Subpopulations ◽  
Cell Subpopulations

scholarly journals Single-cell mass cytometry reveals cross-talk between inflammation-dampening and inflammation-amplifying cells in osteoarthritic cartilage

2020 ◽  
Vol 6 (11) ◽  
pp. eaay5352 ◽  
Author(s):  
Fiorella Carla Grandi ◽  
Reema Baskar ◽  
Piera Smeriglio ◽  
Shravani Murkherjee ◽  
Pier Francesco Indelli ◽  
...  
Keyword(s):  
Single Cell ◽  
Interleukin 1 ◽  
Cell Mass ◽  
Tumor Necrosis Factor Receptor ◽  
Mass Cytometry ◽  
Therapeutic Approaches ◽  
Osteoarthritic Cartilage ◽  
Regenerative Cells ◽  
Cell Subpopulations ◽  
D Cells

Aging or injury leads to degradation of the cartilage matrix and the development of osteoarthritis (OA). Because of a paucity of single-cell studies of OA cartilage, little is known about the interpatient variability in its cellular composition and, more importantly, about the cell subpopulations that drive the disease. Here, we profiled healthy and OA cartilage samples using mass cytometry to establish a single-cell atlas, revealing distinct chondrocyte progenitor and inflammation-modulating subpopulations. These rare populations include an inflammation-amplifying (Inf-A) population, marked by interleukin-1 receptor 1 and tumor necrosis factor receptor II, whose inhibition decreased inflammation, and an inflammation-dampening (Inf-D) population, marked by CD24, which is resistant to inflammation. We devised a pharmacological strategy targeting Inf-A and Inf-D cells that significantly decreased inflammation in OA chondrocytes. Using our atlas, we stratified patients with OA in three groups that are distinguished by the relative proportions of inflammatory to regenerative cells, making it possible to devise precision therapeutic approaches.

scholarly journals Clinical recovery from surgery correlates with single-cell immune signatures

2014 ◽  
Vol 6 (255) ◽  
pp. 255ra131-255ra131 ◽  
Author(s):  
Brice Gaudillière ◽  
Gabriela K. Fragiadakis ◽  
Robert V. Bruggner ◽  
Monica Nicolau ◽  
Rachel Finck ◽  
...  
Keyword(s):  
Single Cell ◽  
Immune Cell ◽  
Cell Mass ◽  
Nuclear Factor Κb ◽  
Surgical Trauma ◽  
Strong Correlations ◽  
Mass Cytometry ◽  
Human Immune System ◽  
Immune Correlates ◽  
Element Binding Protein

Delayed recovery from surgery causes personal suffering and substantial societal and economic costs. Whether immune mechanisms determine recovery after surgical trauma remains ill-defined. Single-cell mass cytometry was applied to serial whole-blood samples from 32 patients undergoing hip replacement to comprehensively characterize the phenotypic and functional immune response to surgical trauma. The simultaneous analysis of 14,000 phosphorylation events in precisely phenotyped immune cell subsets revealed uniform signaling responses among patients, demarcating a surgical immune signature. When regressed against clinical parameters of surgical recovery, including functional impairment and pain, strong correlations were found with STAT3 (signal transducer and activator of transcription), CREB (adenosine 3′,5′-monophosphate response element–binding protein), and NF-κB (nuclear factor κB) signaling responses in subsets of CD14+ monocytes (R = 0.7 to 0.8, false discovery rate <0.01). These sentinel results demonstrate the capacity of mass cytometry to survey the human immune system in a relevant clinical context. The mechanistically derived immune correlates point to diagnostic signatures, and potential therapeutic targets, that could postoperatively improve patient recovery.

scholarly journals Uncomplicated Diverticular Disease: Innate and Adaptive Immunity in Human Gut Mucosa before and after Rifaximin

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Rossella Cianci ◽  
Simona Frosali ◽  
Danilo Pagliari ◽  
Paola Cesaro ◽  
Lucio Petruzziello ◽  
...  
Keyword(s):  
Diverticular Disease ◽  
Immune Cell ◽  
End Of Treatment ◽  
Before And After ◽  
Gut Mucosa ◽  
Immune Cell Subpopulations ◽  
Cell Subpopulations ◽  
Uncomplicated Diverticular Disease ◽  
Asymptomatic Subjects

Background/Aim. Uncomplicated diverticular disease (UDD) is a frequent condition in adults. The pathogenesis of symptoms remains unknown. Bacteria are able to interact with Toll-like receptors (TLRs) and to induce inflammation through both innate immunity and T-cell recruitment. We investigated the pattern of TLRs 2 and 4 and the intestinal homing in patients with UDD before and after a course of Rifaximin.Methods. Forty consecutive patients with UDD and 20 healthy asymptomatic subjects were enrolled. Among UDD patients, 20 were assigned to a 2-month course of treatment with Rifaximin 1.2 g/day for 15 days/month and 20 received placebo. Blood sample and colonic biopsies were obtained from patients and controls. The samples were collected and analyzed at baseline and at the end of treatment. Flow cytometry was performed using monoclonal antibodies (CD3, CD4, CD8, CD103, TCR-gamma/delta, CD14, TLR2, and TLR4).Results. In UDD, TLR2 and TLR4 expression on immune cell subpopulations from blood and mucosa of the affected colon are altered as compared with controls. Rifaximin treatment induced significant modifications of altered conditions.Conclusions. Our data show the role of TLRs in the development of inflammation in UDD. TLRs distribution is altered in UDD and these alterations are reversed after antibiotic treatment. This trial is registered with ClinicalTrials.gov:NCT02068482.

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