Aberrant Expression of Novel Cytokine IL-38 and Regulatory T Lymphocytes in Childhood Asthma

Molecules. 2016 Jul 18;21(7):933. doi: 10.3390/molecules21070933.

Abstract

We investigated the expression of novel anti-inflammatory interleukin (IL)-38 and regulatory T (Treg) lymphocytes in childhood asthma patients. The protein and mRNA expression level of IL-38, periostin, peripheral CD4⁺CD25⁺CD134⁺ T lymphocytes as well as CD4⁺CD25(high)FoxP3⁺ and CD4⁺CD25(high)CD127(-) Treg lymphocytes from 40 asthmatic patients and 20 normal control (NC) subjects were studied using ELISA, qPCR and flow cytometry. Serum and supernatant cytokines/chemokines were determined by multiplex assay. Serum IL-38, IL-5, IL-17, IL-6, interferon-γ, periostin, IL-1β and IL-13 concentrations were significantly higher in asthmatic patients with or without steroid treatment than those in controls (all p < 0.05). The percentages of both CD4⁺CD25(high)FoxP3⁺ and CD4⁺CD25(high)CD127(-) Treg lymphocytes were markedly decreased in asthmatic patients with and without steroid treatment than those in controls (all p < 0.05). The elevated IL-38 concentration negatively correlated with the percentage of Treg lymphocytes in asthmatic patients with high level (>40 ng/mL) of periostin (p < 0.05). Although the comparable mRNA levels of IL-38 and its receptor IL-36R were found between patients and controls, the mRNA level of IL-38 positively correlated with IL-36R and negatively correlated with IL-10 in all asthmatic patients (both p < 0.05). The percentage of CD4⁺CD25⁺CD134⁺ activated T lymphocytes was also significantly higher in asthmatic patients with steroid treatment than those in controls (p < 0.05). This cross-sectional study demonstrated that the overexpression of circulating IL-38 may play a role in the immunopathogenesis in asthma.

Keywords: IL-38; childhood asthma; cytokines; regulatory T lymphocytes.

MeSH terms

  • Allergens / immunology
  • Animals
  • Asthma / drug therapy
  • Asthma / genetics*
  • Asthma / immunology*
  • Asthma / metabolism
  • Biomarkers
  • Child
  • Female
  • Gene Expression*
  • Humans
  • Immunoglobulin E / blood
  • Immunoglobulin E / immunology
  • Immunophenotyping
  • Interleukins / blood
  • Interleukins / genetics*
  • Lymphocyte Activation
  • Lymphocyte Count
  • Male
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism*

Substances

  • Allergens
  • Biomarkers
  • IL-38 protein, human
  • Interleukins
  • RNA, Messenger
  • Immunoglobulin E