Genetic ablation of the src kinase p59fynT exacerbates pulmonary inflammation in an allergic mouse model

Am J Respir Cell Mol Biol. 2001 Apr;24(4):469-74. doi: 10.1165/ajrcmb.24.4.4266.


p59fynT is a protein tyrosine kinase in the src family that has been associated with and believed to function in the signaling of many receptors, including the T-cell receptor. A role for the kinase in antigen-driven pulmonary inflammation was examined using mice whose p59fynT gene had been genetically ablated. FynKO mice that were sensitized to ovalbumin exhibited a marked increase in bronchoalveolar lavage eosinophils and cytokines, including interleukin (IL)-4 and IL-5, relative to wild-type mice in response to antigen aerosol exposure. Ovalbumin-stimulated IL-5 production was also increased in cultured splenocytes derived from fynKO mice relative to wild-type mice, whereas interferon-gamma levels were unchanged. Diminished concanavalin A--stimulated IL-4 levels from fynKO splenocytes were consistent with reduced serum immunoglobulin (Ig)E levels observed in sensitized/saline aerosol-challenged animals and may reflect defective natural killer 1.1(+) T cell development. Normalization of IgE levels in sensitized fynKO mice relative to wild-type mice occurred after repeat antigen challenge, which suggests a secondary source of IL-4. Overall, these data demonstrate fyn is a negative regulator of allergic airway inflammation in mice because its absence promotes a shift to a T helper-2 phenotype that may reflect the kinase's role in T-cell receptor signaling.

MeSH terms

  • Animals
  • Antigens / immunology
  • Antigens / pharmacology
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoalveolar Lavage Fluid / immunology
  • Concanavalin A / pharmacology
  • Disease Models, Animal
  • Eosinophils / immunology
  • Hypersensitivity / immunology
  • Hypersensitivity / metabolism*
  • Immunoglobulin E / blood
  • Interleukin-4 / biosynthesis
  • Interleukin-5 / biosynthesis
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Ovalbumin / immunology
  • Ovalbumin / pharmacology
  • Pneumonia / immunology
  • Pneumonia / metabolism*
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / immunology
  • Proto-Oncogene Proteins c-fyn
  • Spleen / cytology
  • Spleen / immunology
  • Th2 Cells / immunology
  • Th2 Cells / metabolism
  • src-Family Kinases / genetics*
  • src-Family Kinases / immunology


  • Antigens
  • Interleukin-5
  • Proto-Oncogene Proteins
  • Concanavalin A
  • Interleukin-4
  • Immunoglobulin E
  • Ovalbumin
  • Fyn protein, mouse
  • Proto-Oncogene Proteins c-fyn
  • src-Family Kinases