Schnurri-2 regulates Th2-dependent airway inflammation and airway hyperresponsiveness

Int Immunol. 2007 Jun;19(6):755-62. doi: 10.1093/intimm/dxm042. Epub 2007 May 9.

Abstract

Schnurri (Shn)-2 is a large zinc finger-containing protein, which plays a critical role in cell growth, signal transduction and lymphocyte development. In Shn-2-deficient (Shn-2(-/-)) CD4 T cells, the activation of nuclear factor-kappaB is up-regulated and their ability to differentiate into Th2 is enhanced. Here, we extend our investigation and demonstrate that Shn-2 regulates Th2 responses in vivo using an ovalbumin-induced allergic asthma model. Eosinophilic inflammation, mucus hyperproduction and airway hyperresponsiveness (AHR) were all enhanced in Shn-2(-/-) mice. Moreover, eosinophilic infiltration and AHR were enhanced in mice given a transfer of Shn-2(-/-) effector Th2. Shn-2 in Th2 is thus considered to play an important role as a negative regulator in allergic airway inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Asthma / immunology
  • Asthma / pathology
  • Asthma / physiopathology
  • Bronchoalveolar Lavage Fluid / chemistry
  • Bronchoalveolar Lavage Fluid / cytology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / pathology
  • Cell Count
  • Chemokine CCL17
  • Chemokine CCL22
  • Chemokines, CC / genetics
  • Chemokines, CC / metabolism
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / physiology
  • Eosinophils / metabolism
  • Eosinophils / pathology
  • Flow Cytometry
  • Gene Expression
  • Interleukin-13 / metabolism
  • Interleukin-5 / metabolism
  • Lung / metabolism
  • Lung / pathology
  • Lung / physiopathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Mice, Transgenic
  • Ovalbumin / immunology
  • Pneumonia / immunology*
  • Pneumonia / pathology
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / immunology
  • Respiratory Hypersensitivity / immunology*
  • Respiratory Hypersensitivity / pathology
  • Respiratory Hypersensitivity / physiopathology
  • Th2 Cells / immunology*
  • Th2 Cells / transplantation
  • Vaccination

Substances

  • Ccl17 protein, mouse
  • Ccl22 protein, mouse
  • Chemokine CCL17
  • Chemokine CCL22
  • Chemokines, CC
  • DNA-Binding Proteins
  • Hivep2 protein, mouse
  • Interleukin-13
  • Interleukin-5
  • Receptors, Antigen, T-Cell, alpha-beta
  • Ovalbumin