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Characterization of IL-6R-expressing monocytes in the lung of patients with chronic obstructive pulmonary disease [THP1]

ABSTRACT: Background: Monocytes play a crucial role in innate immune responses for host defense, yet their involvement in chronic obstructive pulmonary disease (COPD) remains poorly understood. We previously identified a subset of monocytes in COPD lung tissues characterized by high interleukin-6 receptor (IL-6R) expression. This study aimed to characterize the phenotypes of IL-6Rhi monocytes in the lung of COPD patients. Methods: Using flow cytometry, we assessed the abundance of pulmonary CD14+IL-6Rhi cells in never smokers (CNS), control ex-smokers (CES) and COPD patients. IL-6 expression in CD14+ monocytes from peripheral blood of patients with COPD was also examined. CD45+CD206–CD14+IL-6Rhi and CD45+CD206–CD14+IL-6R– cells were isolated from COPD lung tissues for transcriptome analysis. A monocyte line THP1 cell with constitutive IL-6R expression was stimulated with recombinant IL-6, followed by RNA sequencing to evaluate IL-6 responsiveness of IL-6R+ monocytes. Results: The number of pulmonary CD14+IL-6Rhi monocytes was elevated in COPD patients compared to CNS, while CD14+ monocytes in the peripheral blood of COPD patients did not express IL-6R. Upregulated mRNA expression in CD14+IL-6Rhi monocytes was associated with chemotaxis, monocyte differentiation, fatty acid metabolism and integrin-mediated signaling pathway. Stimulation of THP1 cells with recombinant IL-6 induced gene expression changes linked to chemotaxis and organism development. Conclusion: In patients with COPD, CD14+IL-6Rhi monocytes increase in lung tissues compared to CNS and exhibit a different transcriptome profile from CD14+IL-6R– monocytes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE265855 | GEO | 2024/08/21

REPOSITORIES: GEO

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Characterization of IL-6R-expressing monocytes in the lung of patients with chronic obstructive pulmonary disease [IL-6 mono]

Project description:Background: Monocytes play a crucial role in innate immune responses for host defense, yet their involvement in chronic obstructive pulmonary disease (COPD) remains poorly understood. We previously identified a subset of monocytes in COPD lung tissues characterized by high interleukin-6 receptor (IL-6R) expression. This study aimed to characterize the phenotypes of IL-6Rhi monocytes in the lung of COPD patients. Methods: Using flow cytometry, we assessed the abundance of pulmonary CD14+IL-6Rhi cells in never smokers (CNS), control ex-smokers (CES) and COPD patients. IL-6 expression in CD14+ monocytes from peripheral blood of patients with COPD was also examined. CD45+CD206–CD14+IL-6Rhi and CD45+CD206–CD14+IL-6R– cells were isolated from COPD lung tissues for transcriptome analysis. A monocyte line THP1 cell with constitutive IL-6R expression was stimulated with recombinant IL-6, followed by RNA sequencing to evaluate IL-6 responsiveness of IL-6R+ monocytes. Results: The number of pulmonary CD14+IL-6Rhi monocytes was elevated in COPD patients compared to CNS, while CD14+ monocytes in the peripheral blood of COPD patients did not express IL-6R. Upregulated mRNA expression in CD14+IL-6Rhi monocytes was associated with chemotaxis, monocyte differentiation, fatty acid metabolism and integrin-mediated signaling pathway. Stimulation of THP1 cells with recombinant IL-6 induced gene expression changes linked to chemotaxis and organism development. Conclusion: In patients with COPD, CD14+IL-6Rhi monocytes increase in lung tissues compared to CNS and exhibit a different transcriptome profile from CD14+IL-6R– monocytes.

2024-08-21 | GSE265853 | GEO

IL-6R identifies early differentiated human effector memory CD8+ T cells that potently expand and produce IL-2 and IL-13

Project description:We found a unique subset of effector memory (EM) CD8+ T cells that expressed high levels of IL-6 receptor in human peripheral blood. These cells which also expressed high levels of IL-7Ra (referred to as IL-6R high IL-7Rahigh cells) had the a distinct gene expression profile and cellular characteristics compared to other EM CD8+ T cells. IL-6R high IL-7Ra high cells were early differentiated EM CD8+ T cells with decreased expression of T-bet, KLRG1, perforin and granzyme B. These cells had increased cell proliferation likely secondary to enhanced IL-2 production and high affinity IL-2R expression. IL-6R high IL-7Ra high EM CD8+ T cells exclusively produced high levels of IL-2, IL-5, IL-9 and IL-13 although IFN-r was produced by this cell subset and other EM CD8+ T cells. Of interest, IL-6R high IL-7Ra high EM CD8+ T cells expanded in the peripheral blood of patients with chronic obstructive pulmonary disease (COPD) and asthma where CD8+ T cells, IL-13 and IFN-r are suggested to be involved in the pathogenesis. Being the early-differentiated EM CD8+ T cells with a potent capacity to proliferate, survive and generate multiple cytokines, IL-6R high IL-7Ra high EM CD8+ T cells may serve as a primary reservoir for effector CD8+ T cells which potently expand and produce cytokines upon immune stimulation. Duplicate experiments were performed for each condition. In each condition, we independently prepared total RNA using the RNeasy mini kit (Qiagen) and assessed RNA integrity using Bioanalyzer 2100 (Agilent)- RINs were close to 10 for all samples. RNA was then amplified and hybridized to the Illumina HumanHT-12 v4.0 BeadChip, according to Illumina standard protocols.

2012-12-31 | E-GEOD-34562 | biostudies-arrayexpress

Single-cell RNAseq analysis (10X Genomics Chromium) of residual bronchoalveolar lavage fluids in healthy, fumer and COPD patients

Project description:Rationale: Alveolar macrophages (AM) are functionally important innate cells involved in lung homeostasis and immunity. However, it remains unclear whether ontogenically and functionally distinct subpopulations of AM can be found in healthy human airways, and to what extent conditions like smoking or chronic obstructive pulmonary disease (COPD) trigger changes in the AM compartment. Objective: To explore the phenotypical, ontological, transcriptional and functional diversity of human AM isolated from healthy non-smokers, healthy smokers and COPD patients. Methods: We analyzed bronchoalveolar lavage fluid (BALF) cells by flow cytometry, bulk and single-cell(sc) RNA-sequencing (RNA-seq). Main Results: We found that BALF CD206 + macrophage subpopulations could be distinguished based on their level of auto-fluorescence. CD206 + autofluorescent high (AF hi ) AM were identified as classical self-proliferative AM, while autofluorescent low (AF lo ) AM originated from monocytes and were expressing both monocyte- and classical AM-related genes. Of note, monocyte-derived AF lo AM were equally represented in each category of subjects and exhibited a functionally distinct immunoregulatory profile, including the ability to secrete the immunosuppressive cytokine interleukin-10 (IL-10). Finally, we provide evidence that the monocyte-associated marker CCR2 can be used by flow cytometry to distinguish AM according to their origin.

2022-05-23 | GSE183974 | GEO

Characterization of two lung alveolar macrophages in bronchoalveolar lavage fluid (BALF) cells in non-fumer healthy, fumer and COPD patients

2022-05-23 | GSE183973 | GEO

Characterization of IL-6R-expressing monocytes in the lung of patients with chronic obstructive pulmonary disease [IL-6 mono]

Project description:Characterization of IL-6R-expressing monocytes in the lung of patients with chronic obstructive pulmonary disease [IL-6 mono]

| PRJNA1104544 | ENA

Characterization of IL-6R-expressing monocytes in the lung of patients with chronic obstructive pulmonary disease [THP1]

Project description:Characterization of IL-6R-expressing monocytes in the lung of patients with chronic obstructive pulmonary disease [THP1]

| PRJNA1104555 | ENA

IL-6R identifies early differentiated human effector memory CD8+ T cells that potently expand and produce IL-2 and IL-13

2012-12-31 | GSE34562 | GEO

The immunomodulatory effects of periostin on monocyte-derived macrophages

Project description:To explore the effects of periostin on tumor-associated macrophagess, we first sorted CD14+ monocytes from peripheral blood mononuclear cells of healthy donors using magnetic-activated cell sorting and then induced their differentiation into macrophages by culture with M-CSF for 5 days. In the absence of IL-4 stimulation, these macrophages expressed CD163 and Arg1 (a marker of M2 macrophage activation) but not CD206, suggesting that they were similar to macrophages in the early stage of mycosis fungoides (low frequency of CD206+ cells and low IL-4 expression). We then stimulated these macrophages with or without 100 ng/ml of periostin for 6 hours and examined gene expression using a cDNA microarray. Periostin stimulated gene expression on monocyte-derived macrophages was measured at 6 hours after exposure to doses of 100 ng/ml periostin.

2015-07-14 | E-GEOD-70821 | biostudies-arrayexpress

trancription profiling by array of human pulmonary and circulating CD8 cells in COPD

Project description:Background: CD8 cells seem to play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, relatively little is known about their phenotype and function. Aims: To define the transcriptome of pulmonary CD8 cells in COPD and compare to paired circulating CD8 cells and smoker control pulmonary CD8 cells. COPD was defined according to the Global initiative for chronic Obstructive Lung Disease guidelines. Severity of disease was defined according to the patients lung function. In particular the forced evpiratroy volume in 1 second (FEV1).

2013-08-01 | E-MTAB-1688 | biostudies-arrayexpress

Isolated Blood Immune Cell Transcriptomics in COPD

Project description:We observed separation of COPD patients from control smokers by CD4+ T cell transcriptomics. In contrast to CD4+ T cells, there were no transcript differences in whole blood, CD8+ T cells or CD14+ monocytes.

2016-04-15 | GSE56767 | GEO

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