- Title
- Ym1/2 promotes Th2 cytokine expression by inhibiting 12/15(S)-lipoxygenase: identification of a novel pathway for regulating allergic inflammation
- Creator
- Cai, Yeping; Kumar, Rakesh K.; Zhou, Jiansheng; Foster, Paul S.; Webb, Dianne C.
- Relation
- Journal of Immunology Vol. 182, Issue 9, p. 5393-5399
- Publisher Link
- http://dx.doi.org/10.4049/jimmunol.0803874
- Publisher
- American Association of Immunologists
- Resource Type
- journal article
- Date
- 2009
- Description
- 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.
- Subject
- Ym1/2; allergic airways diseases; Th2 cytokines; IL-13
- Identifier
- uon:7312
- Identifier
- http://hdl.handle.net/1959.13/807136
- Identifier
- ISSN:0022-1767
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