Ym1/2 promotes Th2 cytokine expression by inhibiting 12/15(S)-lipoxygenase: identification of a novel pathway for regulating allergic inflammation

J Immunol. 2009 May 1;182(9):5393-9. doi: 10.4049/jimmunol.0803874.


The Ym1/2 lectin is expressed abundantly in the allergic mouse lung in an IL-13-dependent manner. However, the role of Ym1/2 in the development of allergic airways disease is largely unknown. In this investigation, we show that treatment of mice with anti-Ym1/2 Ab during induction of allergic airways disease attenuated mediastinal lymph node production of IL-5 and IL-13. Ym1/2 was found to be expressed by dendritic cells (DCs) in an IL-13-dependent manner and supplementation of DC/CD4(+) T cell cocultures with Ym1/2 enhanced the ability of IL-13(-/-) DCs to stimulate the secretion of IL-5 and IL-13. Affinity chromatography identified 12/15(S)-lipoxygenase (12/15-LOX) as a Ym1/2-interacting protein and functional studies suggested that Ym1/2 promoted the ability of DCs to stimulate cytokine production by inhibiting 12/15-LOX-mediated catalysis of 12-hydroxyeicosatetraenoic acid (12(S)-HETE). Treatment of DC/CD4(+) T cell cultures with the 12/15-LOX inhibitor baicalein enhanced, whereas 12(S)-HETE inhibited the production of Th2 cytokines. Notably, delivery of 12(S)-HETE to the airways of mice significantly attenuated the development of allergic airways inflammation and the production of IL-5 and IL-13. In summary, our results suggest that production of Ym1/2 in response to IL-13 promotes Th2 cytokine production and allergic airways inflammation by inhibiting the production of 12(S)-HETE by 12/15-LOX.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arachidonate 12-Lipoxygenase / metabolism
  • Arachidonate 15-Lipoxygenase / metabolism
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / pathology
  • Cells, Cultured
  • Chitinases / biosynthesis
  • Chitinases / genetics
  • Chitinases / physiology*
  • Coculture Techniques
  • Cytokines / antagonists & inhibitors
  • Cytokines / biosynthesis*
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Dendritic Cells / pathology
  • Eosinophilia / enzymology
  • Eosinophilia / pathology
  • Eosinophilia / prevention & control*
  • Inflammation Mediators / physiology*
  • Interleukin-13 / deficiency
  • Interleukin-13 / genetics
  • Interleukin-13 / physiology
  • Lectins / biosynthesis
  • Lectins / genetics
  • Lectins / physiology*
  • Lipoxygenase Inhibitors*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Signal Transduction / immunology*
  • Th2 Cells / enzymology
  • Th2 Cells / immunology*
  • Th2 Cells / pathology
  • beta-N-Acetylhexosaminidases / biosynthesis
  • beta-N-Acetylhexosaminidases / genetics
  • beta-N-Acetylhexosaminidases / physiology*


  • 12-15-lipoxygenase
  • Cytokines
  • Inflammation Mediators
  • Interleukin-13
  • Lectins
  • Lipoxygenase Inhibitors
  • Arachidonate 12-Lipoxygenase
  • Arachidonate 15-Lipoxygenase
  • Chitinases
  • Ym2 protein, mouse
  • Chil3 protein, mouse
  • beta-N-Acetylhexosaminidases