scholarly journals TLR-2 expression and dysregulated human Treg/Th17 phenotype in Aspergillus flavus infected patients of chronic rhinosinusitis with nasal polyposis

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Gargi Rai ◽  
Shukla Das ◽  
Mohammad Ahmad Ansari ◽  
Praveen Kumar Singh ◽  
Sajad Ahmad Dar ◽  
...  
Keyword(s):  
Chronic Rhinosinusitis ◽  
Aspergillus Flavus ◽  
Nasal Polyposis ◽  
Mononuclear Cells ◽  
Transforming Growth Factor ◽  
Critical Role ◽  
Treg Cells ◽  
Peripheral Blood Mononuclear ◽  
Immune Imbalance

Abstract Background T helper (Th)17 and regulatory T (Treg) cells with toll-like receptor (TLR)-2 have been acknowledged to play a critical role in chronic rhinosinusitis with nasal polyposis (CRSwNP). However, its pathogenesis has been perplexed by conflicting reports on the role of Th17/Treg cells in patients of distinct ethnicities. We attempted to understand the role of Th responses induced during host defense against Aspergillus flavus. Results The percentages of Th17 (CD4+CD161+IL23R+) and Treg (CD4+CD25+FoxP3+) cell populations and various cytokine profiles in peripheral blood mononuclear cells (PBMCs) challenged by A. flavus antigens were characterized from 50 CRSwNP cases, before and after treatment, and in 50 healthy controls. TLR-2 expression was analyzed in tissues of cases and controls for disease co-relation. The major pathogen identified in our study was A. flavus by mycological investigations. A marked immune imbalance was noted with elevated Th17 and decreased Tregs in PBMCs of CRSwNP patients after A. flavus stimulation. Comparatively, interleukin (IL)-17 and IL-10 levels were increased, with low transforming growth factor (TGF)-β levels in A. flavus stimulated PBMC supernatants of patients. The mRNA expression of TLR-2 in polyps of CRSwNP patients indicated significant (p = 0.001) upregulation in comparison to the controls. Conclusions Our data highlights the excessive expression of TLR-2 in nasal polyps contributing to the imbalance in Th17/Tregs population in patients. After therapy, recovery of Tregs cells indicates restoration and tissue homeostasis, though high circulating CD4+CD161+ Th17 cells may continue to be a threat to patients predisposed to future recurrences. The constant exposure and tendency of A. flavus to colonize nasal cavities can lead to a Th17 driven airway inflammation. Dysregulated Th17 with TLR-2 promote resistance to treatment and progression to the chronicity of the disease.

scholarly journals Role of T cells in intrauterine administration of activated peripheral blood mononuclear cells in recurrent implantation failure.

2021 ◽  
Author(s):  
Guillaume Ricaud ◽  
Cathy Vaillancourt ◽  
Veronique Blais ◽  
Marjorie Disdier ◽  
Fabien Joao ◽  
...  
Keyword(s):  
T Cells ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Treg Cells ◽  
Implantation Failure ◽  
Recurrent Implantation Failure ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

Intrauterine administration of autologous peripheral blood mononuclear cells (PBMC) has been recently proposed as new immunotherapy for patients with unexplained recurrent implantation failure (RIF). In these patients, administration of activated PBMC 24-h or 72-h before embryo transfer resulted in a 3-fold increase in biochemical pregnancy rate. In this study we evaluated the role of T cells to promotes human endometrial receptivity. On the day of ovulation, PBMC were isolated from and activated with T cells mitogen, the phytohemagglutinin (PHA) and hCG for 48-h in a conditioned culture medium. Distributions of CD4+ T cells were characterized in 157 patients by flow cytometry before and after PHA/hCG activation. Cytokine production was analyzed by cytometric beads array. We observed in RIF patients a significant decrease in Th2 and natural Treg cells before activation with PHA/hCG and an increase of Th17 cells after activation compared to intrauterine sperm insemination (IUI) and in vitro fertilization (IVF) groups. Furthermore, the hCG/PHA treatment increases anti-inflammatory T cells (Th2 and Treg cells) compared to non-treated T cells. Principal component analysis (PCA) performed on CD4 T cell subtypes revealed a different cellular profile in the RIF compared to the IUI and IVF groups. This inflammatory state change could explain how endometrium immunomodulation by hCG-activated PBMC helps patients with unexplained RIF to reach implantation.

scholarly journals Response Gene to Complement-32 Promotes the Imbalance of Treg/Th17 in Patients with Dilated Cardiomyopathy

2017 ◽  
Vol 43 (4) ◽  
pp. 1515-1525 ◽  
Author(s):  
Bailing Li ◽  
Wei Zhou ◽  
Xiaojun Tang ◽  
Wei Wang ◽  
Jiajun Pan ◽  
...  
Keyword(s):  
Dilated Cardiomyopathy ◽  
Th17 Cells ◽  
Mononuclear Cells ◽  
Sandwich Elisa ◽  
Treg Cells ◽  
Response Gene ◽  
Peripheral Blood Mononuclear ◽  
Healthy Control ◽  
A Cell

Background/Aims: The imbalance of Treg/Th17 cells plays important role in the pathogenesis of dilated cardiomyopathy (DCM). Response gene to complement (RGC)-32 is a cell cycle regulator that plays an important role in cell proliferation. We evaluated whether the upregulation of RGC-32 was implicated in the homeostasis of Treg/Th17 cells in DCM. Methods: The levels of plasma RGC-32, IL-17 and TGF-β1, and the frequencies of circulating CD4+ RGC-32+ T cells, Th17 and Treg cells in patients with DCM were determined by Cytokine-specific sandwich ELISA and the flow cytometer (FCM), respectively. Results: A significant elevation of plasma RGC-32 in patients with DCM compared with healthy control (HC) subjects was observed. This upregulation was associated with an increase in frequency of Th17 and a decrease in frequency of Treg cells. To further assessed the role of RGC-32, we investigated the effects of RGC-32 up- or down-regulation on frequencies of Th17 and Treg cells in peripheral blood mononuclear cells (PBMCs) from subjects. Importantly, overexpression of RGC-32 was accompanied by an augmentation of Th17 and a reduction of Treg expression. Conclusion: In summary, our study demonstrated the up-regulation of RGC-32 contributed to the imbalance of Treg/Th17 cells in patients with DCM.

scholarly journals Myeloid Fbxw7 Prevents Pulmonary Fibrosis by Suppressing TGF-β Production

2022 ◽  
Vol 12 ◽  
Author(s):  
Jia He ◽  
Yue Du ◽  
Gaopeng Li ◽  
Peng Xiao ◽  
Xingzheng Sun ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Mononuclear Cells ◽  
Transforming Growth Factor ◽  
Treatment Options ◽  
Myeloid Cell ◽  
Transforming Growth Factor Β ◽  
Peripheral Blood Mononuclear ◽  
Regulation Mechanisms ◽  
Insight Into

Idiopathic pulmonary fibrosis (IPF) is a group of chronic interstitial pulmonary diseases characterized by an inexorable decline in lung function with limited treatment options. The abnormal expression of transforming growth factor-β (TGF-β) in profibrotic macrophages is linked to severe pulmonary fibrosis, but the regulation mechanisms of TGF-β expression are incompletely understood. We found that decreased expression of E3 ubiquitin ligase Fbxw7 in peripheral blood mononuclear cells (PBMCs) was significantly related to the severity of pulmonary fibrosis in IPF patients. Fbxw7 is identified to be a crucial suppressing factor for pulmonary fibrosis development and progression in a mouse model induced by intratracheal bleomycin treatment. Myeloid cell-specific Fbxw7 deletion increases pulmonary monocyte-macrophages accumulation in lung tissue, and eventually promotes bleomycin-induced collagen deposition and progressive pulmonary fibrosis. Notably, the expression of TGF-β in profibrotic macrophages was significantly upregulated in myeloid cell-specific Fbxw7 deletion mice after bleomycin treatment. C-Jun has long been regarded as a critical transcription factor of Tgfb1, we clarified that Fbxw7 inhibits the expression of TGF-β in profibrotic macrophages by interacting with c-Jun and mediating its K48-linked ubiquitination and degradation. These findings provide insight into the role of Fbxw7 in the regulation of macrophages during the pathogenesis of pulmonary fibrosis.

scholarly journals Expression and Clinical Significance of Mucin Gene in Chronic Rhinosinusitis

2020 ◽  
Vol 20 (11) ◽  
Author(s):  
Jiaxin Tong ◽  
Qingjia Gu
Keyword(s):  
Chronic Rhinosinusitis ◽  
Transforming Growth Factor ◽  
Critical Role ◽  
Transforming Growth Factor Β1 ◽  
Inflammatory Factors ◽  
Human Neutrophil Elastase ◽  
Mucin Expression ◽  
Nasal Disease ◽  
Tgf Β1

Abstract Purpose of Review This review highlights the expression and regulation of mucin in CRS and discusses its clinical implications. Recent Findings Chronic rhinosinusitis (CRS) is common chronic nasal disease; one of its main manifestations and important features is mucus overproduction. Mucin is the major component of mucus and plays a critical role in the pathophysiological changes in CRS. The phenotype of CRS affects the expression of various mucins, especially in nasal polyps (NP). Corticosteroids(CS), human neutrophil elastase (HNE), and transforming growth factor-β1 (TGF-β1) are closely related to the tissue remodeling of CRS and regulate mucin expression, mainly MUC1, MUC4, MUC5AC, and MUC5B. “It is expected that CS, HNE and TGF - β could be used to regulate the expression of mucin in CRS.” However, at present, the research on mucin is mainly focused on mucin 5AC and mucin 5B, which is bad for finding new therapeutic targets. Summary Investigating the expression and location of mucin in nasal mucosa and understanding the role of various inflammatory factors in mucin expression are helpful to figure out regulatory mechanisms of airway mucin hypersecretion. It is of great significance for the treatment of CRS.

scholarly journals Increase of CD4+CD25highFoxP3+ cells impairs in vitro human microbicidal activity against Mycobacterium tuberculosis during latent and acute pulmonary tuberculosis

2021 ◽  
Vol 15 (7) ◽  
pp. e0009605
Author(s):  
Lorenzzo Lyrio Stringari ◽  
Luciana Polaco Covre ◽  
Flávia Dias Coelho da Silva ◽  
Vivian Leite de Oliveira ◽  
Maria Carolina Campana ◽  
...  
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
Mononuclear Cells ◽  
Critical Role ◽  
Latent Tuberculosis ◽  
Treg Cells ◽  
Host Responses ◽  
Peripheral Blood Mononuclear ◽  
Microbicidal Activity

Background Regulatory T cells (Tregs) play a critical role during Mycobacterium tuberculosis (Mtb) infection, modulating host responses while neutralizing excessive inflammation. However, their impact on regulating host protective immunity is not completely understood. Here, we demonstrate that Treg cells abrogate the in vitro microbicidal activity against Mtb. Methods We evaluated the in vitro microbicidal activity of peripheral blood mononuclear cells (PBMCs) from patients with active tuberculosis (TB), individuals with latent tuberculosis infection (LTBI, TST+/IGRA+) and healthy control (HC, TST-/IGRA-) volunteers. PBMCs, depleted or not of CD4+CD25+ T-cells, were analyzed to determine frequency and influence on microbicidal activity during in vitro Mtb infection with four clinical isolates (S1, S5, R3, and R6) and one reference strain (H37Rv). Results The frequency of CD4+CD25highFoxP3+ cells were significantly higher in Mtb infected whole blood cultures from both TB patients and LTBI individuals when compared to HC. Data from CD4+CD25+ T-cells depletion demonstrate that increase of CD4+CD25highFoxP3+ is associated with an impairment of Th-1 responses and a diminished in vitro microbicidal activity of LTBI and TB groups. Conclusions Tregs restrict host anti-mycobacterial immunity during active disease and latent infection and thereby may contribute to both disease progression and pathogen persistence.

scholarly journals Attenuated pulmonary fibrosis in sialidase-3 knockout (Neu3−/−) mice

2020 ◽  
Vol 318 (1) ◽  
pp. L165-L179 ◽  
Author(s):  
Tejas R. Karhadkar ◽  
Wensheng Chen ◽  
Richard H. Gomer
Keyword(s):  
Pulmonary Fibrosis ◽  
Mononuclear Cells ◽  
Transforming Growth Factor ◽  
Human Peripheral Blood ◽  
Lavage Fluid ◽  
Scar Tissue ◽  
Transforming Growth Factor Β1 ◽  
Peripheral Blood Mononuclear ◽  
Male And Female

Pulmonary fibrosis involves the formation of inappropriate scar tissue in the lungs, but what drives fibrosis is unclear. Sialidases (also called neuraminidases) cleave terminal sialic acids from glycoconjugates. In humans and mice, pulmonary fibrosis is associated with desialylation of glycoconjugates and upregulation of sialidases. Of the four mammalian sialidases, we previously detected only NEU3 in the bronchoalveolar lavage fluid from mice with bleomycin-induced pulmonary fibrosis. In this report, we show that NEU3 upregulates extracellular accumulation of the profibrotic cytokines IL-6 and IL-1β, and IL-6 upregulates NEU3 in human peripheral blood mononuclear cells, suggesting that NEU3 may be part of a positive feedback loop potentiating fibrosis. To further elucidate the role of NEU3 in fibrosis, we used bleomycin to induce lung fibrosis in wild-type C57BL/6 and Neu3−/− mice. At 21 days after bleomycin, compared with male and female C57BL/6 mice, male and female Neu3−/− mice had significantly less inflammation, less upregulation of other sialidases and the profibrotic cytokine active transforming growth factor β1, and less fibrosis in the lungs. Our results suggest that NEU3 participates in fibrosis and that NEU3 could be a target to develop treatments for fibrosis.

scholarly journals Kuijieling-Containing Serum Regulates Th17 and Treg Cell Differentiation by Inhibiting STAT3 Signaling In Vitro

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Yu Long ◽  
Yuqing He ◽  
Fengming Jie ◽  
Sixin Li ◽  
Yanli Wu ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
T Cells ◽  
Mononuclear Cells ◽  
Transforming Growth Factor ◽  
Treg Cells ◽  
Orphan Receptor ◽  
Cell Culture Supernatant ◽  
T Helper 17 ◽  
Peripheral Blood Mononuclear

Object. To investigate the effect of Kuijieling (KJL) on the balance between T helper 17 (Th17) and regulatory T (Treg) cells in peripheral blood mononuclear cells (PBMC) in vitro and explore the underlying mechanism. Materials and Methods. PBMCs isolated from rats were stimulated with transforming growth factor-β, interleukin (IL)-6, and IL-23 to induce the imbalance of Th17 and Treg cells and were treated with 10, 5, or 2.5% KJL-containing serum. The proportion of Th17 or Treg cells in CD4+ T cells was analyzed by flow cytometry, the concentrations of IL-17, IL-21, and IL-10 were assayed by ELISA, mRNA expressions of retinoic acid-related orphan receptor γt (RORγt), forkhead box protein 3 (Foxp3), and signal transducer and activator of transcription 3 (STAT3) were quantified by PCR, and phosphorylated STAT3 (p-STAT3) was analyzed by flow cytometry. Results. KJL-containing serum decreased the proportion of Th17 cells and increased the proportion of Treg cells in CD4+ T cells, decreased the concentration of IL-17 and IL-21, enhanced the level of IL-10 in the cell culture supernatant, promoted the expression of Foxp3, and inhibited the levels of RORγt, STAT3, and p-STAT3. Conclusion. KJL suppresses the STAT3 pathway to remedy the imbalance between Th17 and Treg cells.

scholarly journals Regulation of CD4+CD25+FOXP3+ Treg Cells in Systemic Lupus Erythematosus (SLE): Association With miRNAs Expression

2021 ◽  
Author(s):  
Abeer M. El-Maghraby ◽  
Yasser B.M. Ali ◽  
Eman El-maadawy ◽  
Mohamed F. Elshal ◽  
Iman H Bassyouni ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Mononuclear Cells ◽  
Cell Function ◽  
Treg Cells ◽  
Regulatory Function ◽  
Maximum Increase ◽  
Peripheral Blood Mononuclear ◽  
Diagnostic Role ◽  
Mirnas Expression

Abstract Various genetic factors are controlling regulatory cells T (Treg) cell function, such as miRNAs. Interfering in the miRNA synthesis pathway in Treg cells could result in loss of Tregs' regulatory function, leading to the promotion of inflammatory settings and autoimmunity. This study was designed to investigate the role of miRNA in regulating Treg cells in SLE patients. Treg's frequency was determined using flow cytometry in 100 SLE patients’ and100 healthy controls. Expression of miR-21, miR-24, miR125, miR-146a, miR-148a, and miR-155 was estimated in peripheral blood mononuclear cells (PBMCs) using quantitative real-time polymerase chain reaction (qRT-PCR). The ROC curve evaluated the diagnostic role of miRNAs in SLE. A significant elevation (p<0.001) in Treg cells in SLE patients than controls was observed, with a maximum increase inactive SLE cases. SLE patients exhibit a significant increase in miR-21 (p<0.01), miR-148a (p<0.001), miR-146a (p<0.05) and miR-155 (p<0.001) and significant reduction in miR-24 (p<0.001). An insignificant decrease in miR-125 was observed in SLE patients. The best sensitivity and specificity were detected in miR-148a (88%, 70%) at a cutoff value of 1. 065. Tregs were positively correlated with miR-21(r=0.333, p<0.05), miR-146a (r=0.589, p<0.01) and miR-148a (r=0.309, p<0.05). In conclusion, this research provides a piece of novel information regarding Treg cells' in SLE patients. Our results pointed to the substantial role of miRNAs in controlling Treg cells in lupus. To validate our interesting results, more researches are needed.

scholarly journals Deconvolution of monocyte responses in inflammatory bowel disease reveals an IL-1 cytokine network that regulates IL-23 in genetic and acquired IL-10 resistance

Gut ◽  
2020 ◽  
pp. gutjnl-2020-321731
Author(s):  
Dominik Aschenbrenner ◽  
Maria Quaranta ◽  
Soumya Banerjee ◽  
Nicholas Ilott ◽  
Joanneke Jansen ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Personalised Medicine ◽  
Mononuclear Phagocytes ◽  
Cytokine Network ◽  
Peripheral Blood Mononuclear ◽  
Transcriptional Signature ◽  
Inflammatory Monocytes ◽  
Transcriptomic Signature ◽  
Inflammatory Bowel

ObjectiveDysregulated immune responses are the cause of IBDs. Studies in mice and humans suggest a central role of interleukin (IL)-23-producing mononuclear phagocytes in disease pathogenesis. Mechanistic insights into the regulation of IL-23 are prerequisite for selective IL-23 targeting therapies as part of personalised medicine.DesignWe performed transcriptomic analysis to investigate IL-23 expression in human mononuclear phagocytes and peripheral blood mononuclear cells. We investigated the regulation of IL-23 expression and used single-cell RNA sequencing to derive a transcriptomic signature of hyperinflammatory monocytes. Using gene network correlation analysis, we deconvolved this signature into components associated with homeostasis and inflammation in patient biopsy samples.ResultsWe characterised monocyte subsets of healthy individuals and patients with IBD that express IL-23. We identified autosensing and paracrine sensing of IL-1α/IL-1β and IL-10 as key cytokines that control IL-23-producing monocytes. Whereas Mendelian genetic defects in IL-10 receptor signalling induced IL-23 secretion after lipopolysaccharide stimulation, whole bacteria exposure induced IL-23 production in controls via acquired IL-10 signalling resistance. We found a transcriptional signature of IL-23-producing inflammatory monocytes that predicted both disease and resistance to antitumour necrosis factor (TNF) therapy and differentiated that from an IL-23-associated lymphocyte differentiation signature that was present in homeostasis and in disease.ConclusionOur work identifies IL-10 and IL-1 as critical regulators of monocyte IL-23 production. We differentiate homeostatic IL-23 production from hyperinflammation-associated IL-23 production in patients with severe ulcerating active Crohn’s disease and anti-TNF treatment non-responsiveness. Altogether, we identify subgroups of patients with IBD that might benefit from IL-23p19 and/or IL-1α/IL-1β-targeting therapies upstream of IL-23.

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