scholarly journals Sexual-dimorphism in human immune system aging

2019 ◽  
Author(s):  
Eladio J. Márquez ◽  
Cheng-han Chung ◽  
Radu Marches ◽  
Robert J. Rossi ◽  
Djamel Nehar-Belaid ◽  
...  
Keyword(s):  
Immune System ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Rna Seq ◽  
Human Immune System ◽  
Peripheral Blood Mononuclear ◽  
Cell Functions ◽  
Age Related ◽  
Male Specific

AbstractDifferences in immune function and responses contribute to health- and life-span disparities between sexes. However, the role of sex in immune system aging is not well understood. Here, we characterize peripheral blood mononuclear cells from 172 healthy adults 22-93 years of age using ATAC-seq, RNA-seq, and flow-cytometry. These data reveal a shared epigenomic signature of aging including declining naïve T cell and increasing monocyte/cytotoxic cell functions. These changes were greater in magnitude in men and accompanied by a male-specific genomic decline in B-cell specific loci. Age-related epigenomic changes first spike around late-thirties with similar timing and magnitude between sexes, whereas the second spike is earlier and stronger in men. Unexpectedly, genomic differences between sexes increase after age 65, with men having higher innate and pro-inflammatory activity and lower adaptive activity. Impact of age and sex on immune cell genomes can be visualized at https://immune-aging.jax.org to provide insights into future studies.

scholarly journals Gene Expression Analysis Reveals Age and Ethnicity Signatures Between Young and Old Adults in Human PBMC

2021 ◽  
Author(s):  
Yang Hu ◽  
Yudai Xu ◽  
Lipeng Mao ◽  
Wen Lei ◽  
Jan Jian Xiang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune System ◽  
Large Scale ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Human Immune System ◽  
Immune Systems ◽  
Network Analyses ◽  
Age Related ◽  
Human Immune

Abstract Background: Human immune system functions over an entire lifetime, yet how and why the immune system becomes less effective with age are not well understood. Therefore, the aim of this study is to exploit a large-scale population-based strategy to systematically identify genes and pathways differentially expressed as a function of chronological age. Despite the importance of age and race in shaping immune cell numbers and functions, it is unclear whether Asian and Caucasian immune systems go through similar gene expression changes throughout their lifespan, and to what extent these aging-associated variations are shared among ethnicities. Results: Here, we characterize peripheral blood mononuclear cells transcriptome from 19 healthy adults of RNA-seq data and 153 healthy subjects of micoarray data with 21~90 years of age using the weighted gene correlation network analyses (WGCNA). These data reveal a set of insightful gene expression modules and representative gene biomarkers for human immune system aging from Asian and Caucasian ancestry, respectively. Among them, the aging-specific modules may show an age-related gene expression variation spike around early-seventies. In addition, we find the top hub genes including NUDT7, CLPB, OXNAD1 and MLLT3 are shared between Asian and Caucasian aging related modules and further validated in human PBMCs from different age groups. Conclusion: Overall, our findings reveal how age and race differentially affect the immune systems between Asian and Caucasian, as well as discovered a common genetic variant that greatly impacts normal PBMC aging between Asian and Caucasian.

scholarly journals Identification of age and ethnicity specific gene expression biomarkers for immune aging

2021 ◽  
Author(s):  
Yang Hu ◽  
Yudai Xu ◽  
Lipeng Mao ◽  
Wen Lei ◽  
Jian Xiang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune System ◽  
Mononuclear Cells ◽  
Specific Gene ◽  
Human Immune System ◽  
Peripheral Blood Mononuclear ◽  
Network Analyses ◽  
Age Related ◽  
Human Immune ◽  
The Impact

ABSTRACTHuman immune system functions over an entire lifetime, yet how and why the immune system becomes less effective with age are not well understood. Here, we characterize peripheral blood mononuclear cells transcriptome from 172 healthy adults with 21~90 years of age using RNA-seq and the weighted gene correlation network analyses (WGCNA). These data reveal a set of insightful gene expression modules and representative gene biomarkers for human immune system aging from Asian and Caucasian ancestry, respectively. Among them, the aging-specific modules show an age-related gene expression variation spike around early-seventies. In addition, it is not known whether Asian and Caucasian immune systems go through similar gene expression changes throughout their lifespan, and to what extent these aging-associated changes are shared among ethnicities. We find the top hub genes including NUDT7, CLPB, OXNAD1 and MLLT3 are shared between Asian and Caucasian aging related modules and further validated in human PBMCs from different age groups. Overall, the impact of age and race on transcriptional variation elucidated from this study provide insights into the transcriptional driver of immune aging.

scholarly journals Acetate correlates with disability and immune response in multiple sclerosis

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e10220 ◽  
Author(s):  
Silvia Pérez-Pérez ◽  
María Inmaculada Domínguez-Mozo ◽  
Aitana Alonso-Gómez ◽  
Silvia Medina ◽  
Noelia Villarrubia ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Short Chain Fatty Acids ◽  
Liquid Chromatography Mass Spectrometry ◽  
Peripheral Blood Mononuclear ◽  
Healthy Donors ◽  
Disability Status

Background Gut microbiota has been related to multiple sclerosis (MS) etiopathogenesis. Short-chain fatty acids (SCFA) are compounds derived from microbial metabolism that have a role in gut-brain axis. Objectives To analyse SCFA levels in plasma of MS patients and healthy donors (HD), and the possible link between these levels and both clinical data and immune cell populations. Methods Ninety-five MS patients and 54 HD were recruited. Patients were selected according to their score in the Expanded Disability Status Scale (EDSS) (49 EDSS ≤ 1.5, 46 EDSS ≥ 5.0). SCFA were studied in plasma samples by liquid chromatography-mass spectrometry. Peripheral blood mononuclear cells were studied by flow cytometry. Gender, age, treatments, EDSS and Multiple Sclerosis Severity Score (MSSS) were evaluated at the recruitment. Results Plasma acetate levels were higher in patients than in HD (p = 0.003). Patients with EDSS ≥ 5.0 had higher acetate levels than those with EDSS≤ 1.5 (p = 0.029), and HD (p = 2.97e–4). Acetate levels correlated with EDSS (r = 0.387; p = 1.08e–4) and MSSS (r = 0.265; p = 0.011). In untreated MS patients, acetate levels correlated inversely with CD4+ naïve T cells (r =  − 0.550, p = 0.001) and directly with CD8+ IL-17+ cells (r = 0.557; p = 0.001). Conclusions Plasma acetate levels are higher in MS patients than in HD. In MS there exists a correlation between plasma acetate levels, EDSS and increased IL-17+ T cells. Future studies will elucidate the role of SCFA in the disease.

In vitro cytokine synthesis in unstimulated and mitogen-stimulated peripheral blood mononuclear cells from individuals with schizophrenia

2019 ◽  
Vol 67 (7) ◽  
pp. 1053-1060
Author(s):  
Elżbieta Kozłowska ◽  
Paulina Żelechowska ◽  
Adam Wysokiński ◽  
Paweł Rasmus ◽  
Anna Łucka ◽  
...  
Keyword(s):  
Immune System ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Peripheral Blood Mononuclear ◽  
Spontaneous Production ◽  
Blood Mononuclear Cells ◽  
Ifn Γ

Increasing evidence has shown that the immune system is involved in the schizophrenia development, with alterations in immune cell reactivity being one possible factor contributing to its pathogenesis. The purpose of the study was to evaluate in vitro the capability of peripheral blood mononuclear cells (PBMCs) obtained from subjects with schizophrenia and controls to engage in spontaneous and phytohemagglutinin (PHA)-stimulated cytokine production. The concentrations of various cytokines (interleukin (IL)-1β, IL-17A, tumor necrosis factor (TNF), interferon (IFN)-γ and IL-10) in supernatants from cultured PBMCs were measured using the cytometric bead array. No significant differences in the spontaneous production of IL-1β, IL-17A, IFN-γ and IL-10 by PBMCs were detected between individuals with schizophrenia and controls. TNF synthesis by PBMCs was found to be lower among those with schizophrenia. In all subjects and controls, greater cytokine generation was associated with PBMCs treated with PHA compared with those that were not. The PBMCs from people with schizophrenia displayed considerably higher sensitivity to mitogen stimulation, as the production of IL-17A, TNF and IFN-γ was at least threefold of that observed in healthy subjects, which may be driven by antipsychotics taken by patients with schizophrenia. Correlation was observed between spontaneous production of IFN-γ and Positive and Negative Syndrome Scale G subscore (which measures the general symptoms of schizophrenia) and between PHA-stimulated synthesis of IL–17A and G subscore. Our data confirm that the immune system dysregulation may underlie schizophrenia pathophysiology. There is a potential possibility that immunological tests could be used as a diagnostic, therapeutic and side-effects biomarker for schizophrenia, but further studies are needed.

scholarly journals In Vitro Responsiveness of γδ T Cells fromMycobacterium bovis-Infected Cattle to Mycobacterial Antigens: Predominant Involvement of WC1+Cells

2001 ◽  
Vol 69 (1) ◽  
pp. 89-96 ◽  
Author(s):  
Allister J. Smyth ◽  
Michael D. Welsh ◽  
R. Martyn Girvin ◽  
John M. Pollock
Keyword(s):  
T Cells ◽  
Diagnostic Tests ◽  
Protective Immunity ◽  
Cellular Proliferation ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Γδ T Cells ◽  
Peripheral Blood Mononuclear ◽  
Cell Functions

ABSTRACT It is generally accepted that protective immunity against tuberculosis is generated through the cell-mediated immune (CMI) system, and a greater understanding of such responses is required if better vaccines and diagnostic tests are to be developed. γδ T cells form a major proportion of the peripheral blood mononuclear cells (PBMC) in the ruminant system and, considering data from other species, may have a significant role in CMI responses in bovine tuberculosis. This study compared the in vitro responses of αβ and γδ T cells from Mycobacterium bovis-infected and uninfected cattle. The results showed that, following 24 h of culture of PBMC withM. bovis-derived antigens, the majority of γδ T cells from infected animals became highly activated (upregulation of interleukin-2R), while a lower proportion of the αβ T-cell population showed activation. Similar responses were evident to a lesser degree in uninfected animals. Study of the kinetics of this response showed that γδ T cells remained significantly activated for at least 7 days in culture, while activation of αβ T cells declined during that period. Subsequent analysis revealed that the majority of activated γδ T cells expressed WC1, a 215-kDa surface molecule which is not expressed on human or murine γδ T cells. Furthermore, in comparison with what was found for CD4+ T cells, M. bovis antigen was found to induce strong cellular proliferation but relatively little gamma interferon release by purified WC1+ γδ T cells. Overall, while the role of these cells in protective immunity remains unclear, their highly activated status in response to M. bovis suggests an important role in antimycobacterial immunity, and the ability of γδ T cells to influence other immune cell functions remains to be elucidated, particularly in relation to CMI-based diagnostic tests.

scholarly journals Sildenafil does not affect the proliferation of human lymphocytes in the in vitro transplant model

2019 ◽  
Author(s):  
Beata Kaleta
Keyword(s):  
Bone Marrow ◽  
Immune System ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Human Lymphocytes ◽  
Venous Blood ◽  
Human Immune System ◽  
Pde5 Inhibitors ◽  
Trypan Blue Exclusion ◽  
Peripheral Blood Mononuclear

Sildenafil is a selective inhibitor of type 5 phosphodiesterase (PDE5) used in the treatment of erectile dysfunction (ED) and pulmonary arterial hypertension (PAH). Numerous studies revealed beneficial effects of sildenafil use in chronic kidney disease, and also in renal, liver, heart and bone marrow transplant recipients. Some reports suggest that sildenafil modulates function of the immune system, and additionally proliferation of endothelial, bone marrow and cancer cells. Despite the fact that PDE5 inhibitors showed efficacy and safety, it is very important to know whether these drugs have immunomodulatory properties, because are used in patients after organ transplantation. The influence of sildenafil on antigen-induced proliferation of lymphocytes remains currently unknown, thus the aim of the study was to investigate the effects of the drug on human peripheral blood mononuclear cells (PBMCs) proliferation in a mixed lymphocyte reaction (MLR).PBMCs were isolated from venous blood from 30 donors. The proliferation was examined on the DNA synthesis level by measurements of 3H-thymidine incorporation. Cell viability was determined using trypan blue exclusion method.The study demonstated that sildenafil at concentrations of 0.06 µM, 0.6 µM and 6µM did not affect auto- and alloantigen-induced  proliferation of PBMCs and showed no cytotoxic effect. However, further analysis is required to fully understand the role of PDE5 inhibitors in the regulation of human immune system.

scholarly journals A Novel cDNA-uPA/SCID/Rag2-/-/Jak3-/- Mouse Model for Hepatitis Virus Infection and Reconstruction of Human Immune System

2021 ◽  
Author(s):  
Takuro Uchida ◽  
Yuji Teraoka ◽  
Michio Imamura ◽  
Hatsue Fujino ◽  
Atsushi Ono ◽  
...  
Keyword(s):  
Immune System ◽  
Mouse Model ◽  
Mononuclear Cells ◽  
Hepatitis Virus ◽  
Human Leukocyte ◽  
Human Hepatocytes ◽  
Human Immune System ◽  
Peripheral Blood Mononuclear ◽  
Type Plasminogen Activator

Abstract The humanized mouse is a widely used in vivo model for the investigation of pathogenesis and drug development. In this study, we generated new immunodeficiency cDNA-urokinase-type plasminogen activator (uPA)/SCID/Rag2-/-/Jak3-/- mice and established the mouse model with a humanized liver and immune system. Transplantation of human hepatocytes with human leukocyte antigen (HLA)-A24 resulted in establishment of a highly replaced liver in this mouse model. These mice were successfully infected with hepatitis B virus and hepatis C virus (HCV) for a prolonged period and are available for the analysis of the effect of anti-HCV drugs. Administration of peripheral blood mononuclear cells (PBMCs) obtained from a donor with HLA-A24 resulted in the establishment of 22.6–81.3% of human CD45-positive mononuclear cell chimerism in liver infiltrating cells without causing graft versus host disease. When mice were transplanted with human hepatocytes and then administered PBMCs, an alloimmune response between transplanted human hepatocytes and PBMCs occurred, with production of transplanted hepatocyte-specific anti-HLA antibody. The alloimmunity was never inhibited by methylprednisolone nor cyclosporine A. In conclusion, we succeeded in establishing a humanized liver and immune system using a novel cDNA-uPA/SCID/Rag2-/-/Jak3-/- mouse. This model is not only useful to study hepatitis virus virology but also to study alloimmunity.

scholarly journals Single cell transcriptomics reveals opioid usage evokes widespread suppression of antiviral gene program

2019 ◽  
Author(s):  
Tanya T. Karagiannis ◽  
John P. Cleary ◽  
Busra Gok ◽  
Nicholas G. Martin ◽  
Elliot C. Nelson ◽  
...  
Keyword(s):  
Immune System ◽  
Single Cell ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Ex Vivo ◽  
Cell Types ◽  
Short Exposure ◽  
Opioid Use ◽  
Peripheral Blood Mononuclear ◽  
Antiviral Gene

AbstractChronic opioid usage not only causes addiction behavior through the central nervous system (CNS), but it also modulates the peripheral immune system. However, whether opioid usage positively or negatively impacts the immune system is still controversial. In order to understand the immune modulatory effect of opioids in a systematic and unbiased way, we performed single cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) from opioid-dependent individuals and non-dependent controls. We show that chronic opioid usage evokes widespread suppression of interferon-stimulated genes (ISGs) and antiviral gene program in naive monocytes and upon ex vivo stimulation with the pathogen component lipopolysaccharide (LPS) in multiple innate and adaptive immune cell types. Furthermore, scRNA-seq revealed the same phenomenon with in vitro morphine treatment; after just a short exposure to morphine stimulation, we observed the same suppression of antiviral genes in multiple immune cell types. These findings indicate that both acute and chronic opioid exposure may be harmful to our immune system by suppressing the antiviral gene program, our body’s defense response to potential infection. Our results suggest that further characterization of the immune modulatory effects of opioid use is critical to ensure the safety of clinical opioid usage.

scholarly journals Activation of macrophages by lysophosphatidic acid through the lysophosphatidic acid receptor 1 as a novel mechanism in multiple sclerosis pathogenesis

2019 ◽  
Author(s):  
Jennifer Fransson ◽  
Ana Isabel Gómez ◽  
Jesús Romero-Imbroda ◽  
Oscar Fernández ◽  
Laura Leyva ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Lysophosphatidic Acid ◽  
Macrophage Activation ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Human Monocyte ◽  
Wild Type ◽  
Peripheral Blood Mononuclear ◽  
Cell Functions ◽  
Inflammatory Stimuli

AbstractMultiple sclerosis (MS) is a neuro-inflammatory disease for which the pathogenesis remains largely unclear. Lysophosphatidic acid (LPA) is an endogenous phospholipid that is involved in multiple immune cell functions and is dysregulated in MS. Its receptor LPA1 is expressed in macrophages and regulates their activation, which is of interest due to the role of macrophage activation in MS in both destruction and repair.In this study, we studied the viable Malaga variant of LPA1-null mutation as well as pharmaceutical inhibition of LPA1 in mice with experimental autoimmune encephalomyelitis (EAE), a model of MS. LPA1 expression was also analyzed in both wild-type EAE mice and MS patient immune cells. The effect of LPA and LPA1 on macrophage activation was studied in human monocyte-derived macrophages.We show that lack of LPA1 activity induces a milder clinical course in EAE, and that Lpar1 expression in peripheral blood mononuclear cells (PBMCs) correlates with onset of relapses and severity in wild-type EAE mice. We see the same over-expression in PBMCs from MS patients during relapse compared to progressive forms of the disease, and in monocyte-derived macrophages after exposure to pro-inflammatory stimuli. In addition, LPA induced a pro-inflammatory-like response in macrophages through LPA1, providing a plausible way in which LPA and LPA1 dysregulation can lead to the inflammation seen in MS.These data show a new mechanism of LPA signaling in the pathogenesis of MS, prompting further research into its use as a therapeutic target biomarker.

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