Please use this identifier to cite or link to this item: http://hdl.handle.net/1959.13/807136

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