STAT6 deficiency in a mouse model of allergen-induced airways inflammation abolishes eosinophilia but induces infiltration of CD8+ T cells

Clin Exp Allergy. 1999 Jan;29(1):114-23. doi: 10.1046/j.1365-2222.1999.00405.x.

Abstract

Background: The TH2-type cytokines have been reported to contribute to the asthmatic response. STAT6 has an essential role in IL-4 signalling and in production of TH2 cytokines from T cells and is involved in IgE and IgG1 responses after nematode infections, indicating that STAT6 has an important role in allergic diseases.

Objective: In this study we investigated the effects of STAT6 deficiency on allergen-induced airways inflammation in mice.

Methods: Both ovalbumin (OVA)-sensitized STAT6 deficient (STAT6-/-) mice and wild-type C57BL/6 mice were challenged with aerosolized OVA. Changes in inflammatory cell infiltration and cytokine levels in lung tissue as well as serum immunoglobulin levels were analysed in OVA-challenged STAT6-/- and wild-type mice.

Results: The eosinophilia and lung damage normally resulting from aeroallergen challenge were not seen in STAT6-/- mice. Expression of TH2 cytokines (IL-4 and IL-5) in the lung tissue as well as IgE and IgG1 responses after OVA challenge were profoundly reduced in STAT6-/- mice, whereas expression of IFNgamma was the same in STAT6-/- mice and wild-type mice after OVA challenge. Immunocytochemical analysis of T cells showed the infiltration of CD4+ T cells but not CD8+ T cells increased into the lung of wild-type mice after OVA challenge. However, the OVA-exposed STAT6-/- mice demonstrated the infiltration of both CD4+ T cells and CD8+ T cells with a significant increase in percentage and total number of CD8+ T cells compared with OVA-exposed wild-type mice.

Conclusion: These results indicate that factors which signal through STAT6 are important regulators of eosinophilia of allergic airway inflammation, regulating TH2-type cytokine production both in CD4+ T cells and CD8+ T cells.

MeSH terms

  • Allergens / immunology
  • Allergens / pharmacology*
  • Animals
  • Asthma / chemically induced
  • Asthma / metabolism
  • Asthma / physiopathology
  • CD8-Positive T-Lymphocytes / pathology*
  • Cytokines / biosynthesis
  • Disease Models, Animal
  • Eosinophilia / physiopathology*
  • Immunoglobulin E / blood
  • Immunoglobulin E / drug effects
  • Immunoglobulin G / blood
  • Immunoglobulin G / drug effects
  • Inflammation / chemically induced
  • Inflammation / metabolism*
  • Inflammation / physiopathology
  • Interleukin-4 / biosynthesis
  • Interleukin-5 / biosynthesis
  • Lung / drug effects
  • Lung / metabolism
  • Lung / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Ovalbumin / immunology
  • Ovalbumin / pharmacology
  • STAT6 Transcription Factor
  • Th2 Cells / drug effects
  • Th2 Cells / metabolism
  • Trans-Activators / deficiency*
  • Trans-Activators / genetics

Substances

  • Allergens
  • Cytokines
  • Immunoglobulin G
  • Interleukin-5
  • STAT6 Transcription Factor
  • Stat6 protein, mouse
  • Trans-Activators
  • Interleukin-4
  • Immunoglobulin E
  • Ovalbumin