Dataset Information

T-bet and interleukin-27: possible TH1 immunomodulators of sarcoidosis.

ABSTRACT: Sarcoidosis has often been termed an "immune paradox" as there is peripheral anergy to common recall antigens despite pronounced TH1-dominant inflammation at disease sites, such as the lung, with up-regulation of interferon ?, IL-27 and transcription factors. Peripheral blood may reflect the anergic state, while exhaled breath condensate (EBC) analysis may offer insights into the lung disease.A cross-sectional study was conducted to investigate the expression of TH1 cytokines and transcription factors (IFN?, IL-27 and T-bet) in the peripheral blood and/or EBC of sarcoidosis patients and healthy controls. Whole blood and EBC were collected from sarcoidosis patients and healthy controls. TH1 cytokine expression levels were then measured in peripheral blood mononuclear cells (PBMCs) and/or plasma and EBC using quantitative real-time PCR, ELISA and via Western blotting.Compared to healthy controls, PBMC IL-27 mRNA was higher in patients (p = 0.0019). There were no significant differences in plasma IL-27 protein between patients and controls (p = 0.20). T-bet mRNA and protein were lower (p = 0.010 and p = 0.0043, respectively) in patients compared to controls. There were no significant differences in PBMC IFN? mRNA and protein expression (p = 0.68 and p = 0.74, respectively) nor in EBC IL-27 levels.Our data indicate that depressed T-bet mRNA and protein expression could contribute to the peripheral anergy in sarcoidosis and that IL-27 mRNA levels are elevated in the PBMC from those with sarcoidosis.

SUBMITTER: Loke WS

PROVIDER: S-EPMC4568011 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

T-bet and interleukin-27: possible TH1 immunomodulators of sarcoidosis.

Loke Wei Sheng Joshua WS Freeman Araluen A Garthwaite Linda L Prazakova Silvie S Park Mijeong M Hsu Kenneth K Thomas Paul S PS Herbert Cristan C

Inflammopharmacology 20150809 5

<h4>Background</h4>Sarcoidosis has often been termed an "immune paradox" as there is peripheral anergy to common recall antigens despite pronounced TH1-dominant inflammation at disease sites, such as the lung, with up-regulation of interferon γ, IL-27 and transcription factors. Peripheral blood may reflect the anergic state, while exhaled breath condensate (EBC) analysis may offer insights into the lung disease.<h4>Methods</h4>A cross-sectional study was conducted to investigate the expression o ...[more]

PMID: 26254778

Similar Datasets

Project description:IFN-γ-producing CD4+ T (Th1) cells and IL-17-producing CD4+ T (Th17) cells play a critical role in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the immune regulation between Th1 and Th17 cells remains unclear. Previous studies have demonstrated that interleukin-27 (IL-27)/WSX-1 exerted pro- or anti-inflammatory effects in many acute inflammatory diseases by modulating T cell-mediated immune response, but little was known about its role in chronic inflammatory disease, especially in smoking-related lung diseases. Considering IL-27 is an important regulator in T lymphocytes immune responses and was found markedly increased in patients with COPD, we hypothesized that IL-27/WSX-1 may exert immuno-regulatory effects on the differentiation of Th1 and Th17 cells in smoking-related COPD. In this study, we aimed to evaluate the expression of IL-27 in patients with COPD and explore the role of IL-27/WSX-1 on Th1 and Th17 cells differentiation in a smoking mouse model of emphysema. We found that elevated expression of IL-27 was associated with increased proportion of Th1 cells and Th17 cells in patients with COPD and demonstrated parallel findings in cigarette smoke-exposed mice. In addition, cigarette smoke exposure upregulated the expression of IL-27R (WSX-1) by naive CD4+ T cells in mice. In vitro, IL-27 significantly augmented the secretion of IFN-γ by naive CD4+ T cells via a T-bet, p-STAT1, and p-STAT3-dependent manner, but inhibited the production of IL-17 by a ROR-γt and p-STAT1-dependent way. Furthermore, anti-IL27 treatment dramatically decreased the expression of IFN-γ-producing CD4+ T cells in cigarette smoke-exposed mice. These findings proposed that IL-27 has functions for promoting the expression of Th1 cells but inhibiting the expression of Th17 cells in vitro and IL-27 neutralization-attenuated Th1-mediated inflammation in vivo, suggesting targeting IL-27/WSX-1 may provide a new therapeutic approach for smoking-related COPD.

Project description:Background: Interferon-gamma (IFN-γ) is a key mediator of sarcoidosis-related granulomatous inflammation. Previous findings of IFN-γ-producing Th17 cells in bronchoalveolar lavage fluid from sarcoidosis patients invokes the transition of Th17.0 cells to Th17.1 cells in the disease's pathogenesis. Since the T-bet transcription factor is crucial for this transition, the goal of this study was to determine if T-bet expression in Th17.0 cells reflects the extent of granulomatous inflammation in sarcoidosis patients as assessed by clinical outcomes. Methods: Using a case-control study design, we identified two groups of sarcoidosis subjects (total N = 43) with pulmonary function tests (PFTs) that either (1) changed (increased or decreased) longitudinally or (2) were stable. We used flow cytometry to measure the transcription factors T-bet and RORγt in Th1, Th17.0, and Th17.1 cell subsets defined by CCR6, CCR4 and CXCR3 in blood samples. We compared the percentages of T-bet+ cells in RORγt+Th17.0 cells (defined as CCR6+CCR4+CXCR3-) based on subjects' PFT group. We also assessed the relationship between the direction of change in PFTs with the changes in %T-bet+ frequencies using mixed effects modeling. Results: We found that T-bet expression in subjects' RORγt+Th17.0 cells varied based on clinical outcome. The T-bet+ percentage of RORγt+Th17.0 cells was higher in the cases (subject group with PFT changes) as compared to controls (stable group) (27 vs. 16%, p = 0.0040). In comparisons before and after subjects' PFT changes, the T-bet+ frequency of RORγt+Th17.0 cells increased or decreased in the opposite direction of the PFT change. The percentage of these T-bet+ cells was also higher in those with greater numbers of involved organs. Serum levels of interferon-γ-induced chemokines, CXCL9, CXCL10, and CXCL11, and whole blood gene expression of IFN-γ-related genes including GBP1, TAP1, and JAK2 were independently positively associated with the T-bet+ frequencies of RORγt+Th17.0 cells. Conclusions: These data suggest that expression of T-bet in Th17.0 cells could reflect the extent of granulomatous inflammation in sarcoidosis patients because they represent a transition state leading to the Th17.1 cell phenotype. These findings indicate that Th17 plasticity may be part of the disease paradigm.

Dataset Information

T-bet and interleukin-27: possible TH1 immunomodulators of sarcoidosis.

Publications

T-bet and interleukin-27: possible TH1 immunomodulators of sarcoidosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets