Leptin/Osteopontin Axis Regulated Type 2T Helper Cell Response in Allergic Rhinitis with Obesity

EBioMedicine. 2018 Jun:32:43-49. doi: 10.1016/j.ebiom.2018.05.037. Epub 2018 Jun 7.

Abstract

The prevalence of allergic rhinitis (AR) and obesity in children increased concurrently during recent decades. However, the molecular pathway involved in the interaction between obesity and AR is still unclear. We aimed to investigate the interaction between leptin and osteopontin (OPN) and their effect on T helper (TH) response in the development of AR in children. Thirty AR and 30 healthy children with or without obesity were enrolled. Serum leptin and OPN levels were measured and their relationship with TH1/2 cytokines was analyzed. TH cell differentiation and cytokine production in peripheral blood mononuclear cells (PBMCs) stimulated by leptin and/or OPN were analyzed by enzyme linked immunosorbent assay (ELISA). Obese AR mice models were established to verify the effect of obesity on leptin and OPN as well TH regulation. Immunoprecipitation was performed to confirm the interaction between OPN and leptin in CD4+ T cells. Our results showed elevated serum leptin and OPN in AR children correlated with TH2 cytokines expression. Leptin and OPN enhanced TH2 inflammation in house dust mite stimulated PBMCs from AR children synergistically. Obese AR mice showed as more severe inflammatory reaction, symptoms and expression of nasal leptin and OPN compared with other groups. Immunoprecipitation suggested that OPN and leptin may interact with each other and this process may be mediated by α4 integrin and PI3K/AKT pathway in CD4+ T cells. Our data provide evidence that leptin-mediated OPN upregulation promote TH2 inflammation in AR and this process is achieved through the α4 integrin and PI3K/AKT signaling pathways.

Keywords: Allergic rhinitis; Leptin; Obesity; Osteopontin; T helper cell.

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / metabolism
  • Child
  • Female
  • Humans
  • Integrin alpha4 / genetics
  • Integrin alpha4 / metabolism
  • Leptin / genetics*
  • Leukocytes, Mononuclear / metabolism
  • Leukocytes, Mononuclear / pathology
  • Male
  • Mice
  • Mice, Obese
  • Obesity / complications
  • Obesity / genetics*
  • Obesity / metabolism
  • Obesity / pathology
  • Osteopontin / genetics*
  • Phosphatidylinositol 3-Kinases / genetics
  • Proto-Oncogene Proteins c-akt / genetics
  • Rhinitis, Allergic / complications
  • Rhinitis, Allergic / genetics*
  • Rhinitis, Allergic / metabolism
  • Rhinitis, Allergic / pathology
  • Signal Transduction / genetics
  • Th1 Cells / metabolism
  • Th1-Th2 Balance / genetics

Substances

  • Leptin
  • Osteopontin
  • Integrin alpha4
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt