Dataset Information

IL-27 and type 2 immunity in asthmatic patients: association with severity, CXCL9, and signal transducer and activator of transcription signaling.

ABSTRACT:

Background

Severe asthma (SA) can involve both innate and type 2 cytokine-associated adaptive immunity. Although IL-27 has been reported to potentiate TH1 responses (including the chemokine CXCL9) and suppress TH2 responses, its function in asthmatic patients is unknown.

Objective

We sought to evaluate IL-27 expression in human asthma alone and in combination with type 2 immunity to determine the relationship to disease severity and CXCL9 expression. We also sought to model these interactions in vitro in human bronchial epithelial cells.

Methods

Bronchoalveolar lavage cells from 87 participants were evaluated for IL-27 mRNA and protein alone and in association with epithelial CCL26 (a marker of type 2 activation) in relation to asthma severity and CXCL9 mRNA. Human bronchial epithelial cells cultured at the air-liquid interface and stimulated with IL-27 (1-100 ng/mL) with or without IL-13 (1 ng/mL) were evaluated for CXCL9 expression by using quantitative real-time PCR and ELISA. Phosphorylated and total signal transducer and activator of transcription (STAT) 1/3 were detected by means of Western blotting. Small interfering RNA knockdown of STAT1 or STAT3 was performed.

Results

Bronchoalveolar lavage cell IL-27 mRNA and protein levels were increased in asthmatic patients. Patients with evidence for type 2 pathway activation had higher IL-27 expression (P = .02). Combined IL-27 and CCL26 expression associated with more SA and higher CXCL9 expression (P = .004 and P = .007 respectively), whereas IL-27 alone was associated with milder disease. In vitro IL-13 augmented IL-27-induced CXCL9 expression, which appeared to be due to augmented STAT1 activation and reduced STAT3 activation.

Conclusions

IL-27, in combination with a type 2/CCL26 signature, identifies a more SA phenotype, perhaps through combined effects of IL-27 and IL-13 on STAT signaling. Understanding these interactions could lead to new targets for asthma therapy.

SUBMITTER: Xie M

PROVIDER: S-EPMC4324337 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Publications

IL-27 and type 2 immunity in asthmatic patients: association with severity, CXCL9, and signal transducer and activator of transcription signaling.

Xie Min M Mustovich Anthony T AT Jiang Yi Y Trudeau John B JB Ray Anuradha A Ray Prabir P Hu Haizhen H Holguin Fernando F Freeman Bruce B Wenzel Sally E SE

The Journal of allergy and clinical immunology 20141011 2

<h4>Background</h4>Severe asthma (SA) can involve both innate and type 2 cytokine-associated adaptive immunity. Although IL-27 has been reported to potentiate TH1 responses (including the chemokine CXCL9) and suppress TH2 responses, its function in asthmatic patients is unknown.<h4>Objective</h4>We sought to evaluate IL-27 expression in human asthma alone and in combination with type 2 immunity to determine the relationship to disease severity and CXCL9 expression. We also sought to model these ...[more]

PMID: 25312760

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Project description:Background/Objectives: This study aims to investigate whether Signal Transducer and Activator of Transcription 4 (STAT4) influences the anti-tumor immune response and is possibly involved in the initiation or relapse of pituitary adenomas (PAs) by examining STAT4 polymorphisms and serum levels. This research seeks to uncover potential connections that could inform future therapeutic strategies and improve our understanding of PA pathogenesis. Materials and Methods: This study was conducted at the Laboratory of Ophthalmology, Lithuanian University of Health Sciences. DNA was extracted from peripheral venous blood samples, and the genotyping of four STAT4 SNPs (rs7574865, rs10181656, rs7601754, and rs10168266) was performed using real-time PCR with TaqMan® Genotyping assays. The serum STAT4 levels were measured via ELISA, and the optical density was read at 450 nm. Genotype frequencies, allele distributions, and serum STAT4 levels were statistically analyzed to assess associations with pituitary adenoma occurrence. Results: A binary logistic regression revealed that the STAT4 rs7574865 GT + GG genotypes vs. TT were associated with 1.7-fold increased odds of PA occurrence under the dominant genetic model (p = 0.012). The stratification by gender showed no significant associations in females; however, in males, the STAT4 rs10168266 CC + CT genotypes compared to TT were linked to 2.5-fold increased odds of PA under the dominant genetic model (p = 0.005). STAT4 rs10181656, rs7574865, rs7601754, and rs10168266 were analyzed to evaluate the associations with the pituitary adenoma size. We found that the STAT4 rs7574865 GG genotype was statistically significantly less frequent in the macro PA group compared to in the reference group (p = 0.012). For PA relapse, the rs7574865 G allele was less frequent in the PA group without relapse (p = 0.012), and the GT + GG genotypes were associated with a 1.8-fold increase in the PA group without relapse occurrence (p = 0.008). The serum STAT4 levels were higher in the PA patients compared to those of the reference group (p < 0.001). Elevated STAT4 serum levels were observed in PA patients with the STAT4 rs10181656 CC or CG genotypes (CC: p = 0.004; CG: p = 0.023), and with the rs7574865 GG or GT genotypes (GG: p = 0.003; GT: p = 0.021). The PA patients with the STAT4 rs7601754 AA genotype exhibited higher serum levels compared to those of the reference group (p < 0.001). Similarly, higher serum levels were found in the PA patients with the STAT4 rs10168266 CC or CT genotypes (CC: p = 0.004; CT: p = 0.027). A haplotype frequency analysis revealed no statistically significant results. Conclusions: The STAT4 genotypes were significantly associated with the PA occurrence, size, and relapse. Elevated serum STAT4 levels were observed in the PA patients, highlighting its potential role in PA pathogenesis.

Dataset Information

IL-27 and type 2 immunity in asthmatic patients: association with severity, CXCL9, and signal transducer and activator of transcription signaling.

Background

Objective

Methods

Results

Conclusions

Publications

IL-27 and type 2 immunity in asthmatic patients: association with severity, CXCL9, and signal transducer and activator of transcription signaling.

Similar Datasets

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