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Human monocyte subsets are transcriptionally and functionally altered in aging in response to pattern recognition receptor agonists

ABSTRACT: Human monocyte subsets are transcriptionally and functionally altered in aging in response to pattern recognition receptor agonists

PROVIDER: PRJNA369858 | ENA |

REPOSITORIES: ENA

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Human monocyte subsets are transcriptionally and functionally altered in aging in response to pattern recognition receptor agonists [ExVivo]

Project description:Age-related alterations in immunity have been linked to increased incidence of infections and decreased responses to vaccines in the aging population. Human peripheral blood monocytes are known to promote antigen presentation and antiviral activities; however, the impact of aging on monocyte functions remains an open question. We present an in-depth global analysis examining the impact of aging on classical (CD14+CD16-), intermediate (CD14+CD16+), and non-classical (CD14dimCD16+) monocytes. Monocytes sorted from non-frail healthy adults (18-40 yrs) and old (≥ 65 yrs) individuals were analyzed after stimulation with TLR4, TLR7/8, and RIG-I agonists. Our data showed under non-stimulated conditions, monocyte subsets did not reveal significant age-related alternations; however, agonist stimulated-monocytes from adults and old subjects did show differences at the transcriptional and functional levels. These alternations in many immune-related transcripts and biological processes resulted in reduced production of IFNα, IFN, IL-1β, CCL20, and CCL8, and higher expression of CX3CR1 in monocytes from old subjects. Our findings represent a comprehensive analysis of the influence of human aging on pattern recognition receptors signaling and monocyte functions, and have implications for strategies to enhance the immune response in the context of infection and immunization.

2017-07-27 | GSE94497 | GEO

Human monocyte subsets are transcriptionally and functionally altered in aging in response to pattern recognition receptor agonists [InVitro]

Project description:Age-related alterations in immunity have been linked to increased incidence of infections and decreased responses to vaccines in the aging population. Human peripheral blood monocytes are known to promote antigen presentation and antiviral activities; however, the impact of aging on monocyte functions remains an open question. We present an in-depth global analysis examining the impact of aging on classical (CD14+CD16-), intermediate (CD14+CD16+), and non-classical (CD14dimCD16+) monocytes. Monocytes sorted from non-frail healthy adults (18-40 yrs) and OLD (≥ 65 yrs) individuals were analyzed after stimulation with TLR4, TLR7/8, and RIG-I agonists. Our data showed under non-stimulated conditions, monocyte subsets did not reveal significant age-related alternations; however, agonist stimulated-monocytes from adults and OLD subjects did show differences at the transcriptional and functional levels. These alternations in many immune-related transcripts and biological processes resulted in reduced production of IFNα, IFN, IL-1β, CCL20, and CCL8, and higher expression of CX3CR1 in monocytes from OLD subjects. Our findings represent a comprehensive analysis of the influence of human aging on pattern recognition receptors signaling and monocyte functions, and have implications for strategies to enhance the immune response in the context of infection and immunization.

2017-07-27 | GSE94496 | GEO

Human Monocyte Subsets Are Transcriptionally and Functionally Altered in Aging in Response to Pattern Recognition Receptor Agonists.

Project description:Age-related alterations in immunity have been linked to increased incidence of infections and decreased responses to vaccines in the aging population. Human peripheral blood monocytes are known to promote Ag presentation and antiviral activities; however, the impact of aging on monocyte functions remains an open question. We present an in-depth global analysis examining the impact of aging on classical (CD14+CD16-), intermediate (CD14+CD16+), and nonclassical (CD14dimCD16+) monocytes. Monocytes sorted from nonfrail healthy adults (21-40 y) and old (?65 y) individuals were analyzed after stimulation with TLR4, TLR7/8, and retinoic acid-inducible gene I agonists. Our data showed that under nonstimulated conditions, monocyte subsets did not reveal significant age-related alternations; however, agonist stimulated-monocytes from adults and old subjects did show differences at the transcriptional and functional levels. These alternations in many immune-related transcripts and biological processes resulted in reduced production of IFN-?, IFN-?, IL-1?, CCL20, and CCL8, and higher expression of CX3CR1 in monocytes from old subjects. Our findings represent a comprehensive analysis of the influence of human aging on pattern recognition receptors signaling and monocyte functions, and have implications for strategies to enhance the immune response in the context of infection and immunization.

| S-EPMC5548610 | biostudies-literature

Human monocyte subsets are transcriptionally and functionally altered in aging in response to pattern recognition receptor agonists

Project description:This SuperSeries is composed of the SubSeries listed below.

2017-07-26 | GSE94499 | GEO

PD-1-stimulated T cell subsets are transcriptionally and functionally distinct

Project description:PD-1-stimulated T cell subsets are transcriptionally and functionally distinct

| PRJNA731922 | ENA

Human intestinal tissue-resident memory T cells comprise transcriptionally and functionally distinct subsets

Project description:Human intestinal tissue-resident memory T cells comprise transcriptionally and functionally distinct subsets

| PRJNA682612 | ENA

Human intestinal tissue-resident memory T cells comprise transcriptionally and functionally distinct subsets I

Project description:Human intestinal tissue-resident memory T cells comprise transcriptionally and functionally distinct subsets I

| PRJNA682613 | ENA

Human intestinal tissue-resident memory T cells comprise transcriptionally and functionally distinct subsets II

Project description:Human intestinal tissue-resident memory T cells comprise transcriptionally and functionally distinct subsets II

| PRJNA682615 | ENA

PD-1-stimulated T cell subsets are transcriptionally and functionally distinct.

Project description:Despite the obvious inhibitory outcome of PD-1 signaling, an additional series of functions are activated. We have observed that T cells stimulated through the T cell receptor (TCR) and PD-1 primarily do not proliferate; however, there is a population of cells that proliferates more than through TCR stimulation alone. In this study, we performed flow cytometry and RNA sequencing on individual populations of T cells and discovered that unlike naive T cells, which were inhibited following PD-1 ligation, T cells that proliferated more following PD-1 ligation were associated with effector and central memory phenotypes. We showed that these populations had different gene expression profiles following PD-1 ligation with PD-L1 compared to PD-L2. The presence of transcriptionally and functionally distinct T cell populations responsive to PD-1 ligation provides new insights into the biology of PD-1 and suggest the use of T cell subset-specific approaches to improve the clinical outcome of PD-1 blockade.

| S-EPMC8426269 | biostudies-literature

Airway Macrophages Encompass Transcriptionally and Functionally Distinct Subsets Altered by Smoking.

Project description:Alveolar macrophages (AMs) are functionally important innate cells involved in lung homeostasis and immunity and whose diversity in health and disease is a subject of intense investigations. Yet, it remains unclear to what extent conditions like smoking or chronic obstructive pulmonary disease (COPD) trigger changes in the AM compartment. Here, we aimed to explore heterogeneity of human AMs isolated from healthy nonsmokers, smokers without COPD, and smokers with COPD by analyzing BAL fluid cells by flow cytometry and bulk and single-cell RNA sequencing. We found that subpopulations of BAL fluid CD206+ macrophages could be distinguished based on their degree of autofluorescence in each subject analyzed. CD206+ autofluorescenthigh AMs were identified as classical, self-proliferative AM, whereas autofluorescentlow AMs were expressing both monocyte and classical AM-related genes, supportive of a monocytic origin. Of note, monocyte-derived autofluorescentlow AMs exhibited a functionally distinct immunoregulatory profile, including the ability to secrete the immunosuppressive cytokine IL-10. Interestingly, single-cell RNA-sequencing analyses showed that transcriptionally distinct clusters of classical and monocyte-derived AM were uniquely enriched in smokers with and without COPD as compared with healthy nonsmokers. Of note, such smoking-associated clusters exhibited gene signatures enriched in detoxification, oxidative stress, and proinflammatory responses. Our study independently confirms previous reports supporting that monocyte-derived macrophages coexist with classical AM in the airways of healthy subjects and patients with COPD and identifies smoking-associated changes in the AM compartment that may favor COPD initiation or progression.

| S-EPMC9348561 | biostudies-literature

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