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Divergent functions for airway epithelial matrix metalloproteinase 7 and retinoic acid in experimental asthma.

  • Author(s): Goswami, Sangeeta;
  • Angkasekwinai, Pornpimon;
  • Shan, Ming;
  • Greenlee, Kendra J;
  • Barranco, Wade T;
  • Polikepahad, Sumanth;
  • Seryshev, Alexander;
  • Song, Li-zhen;
  • Redding, David;
  • Singh, Bhupinder;
  • Sur, Sanjiv;
  • Woodruff, Prescott;
  • Dong, Chen;
  • Corry, David B;
  • Kheradmand, Farrah
  • et al.

Published Web Location

https://doi.org/10.1038/ni.1719
Abstract

The innate immune response of airway epithelial cells to airborne allergens initiates the development of T cell responses that are central to allergic inflammation. Although proteinase allergens induce the expression of interleukin 25, we show here that epithelial matrix metalloproteinase 7 (MMP7) was expressed during asthma and was required for the maximum activity of interleukin 25 in promoting the differentiation of T helper type 2 cells. Allergen-challenged Mmp7(-/-) mice had less airway hyper-reactivity and production of allergic inflammatory cytokines and higher expression of retinal dehydrogenase 1. Inhibition of retinal dehydrogenase 1 restored the asthma phenotype of Mmp7(-/-) mice and inhibited the responses of lung regulatory T cells, whereas exogenous administration of retinoic acid attenuated the asthma phenotype. Thus, MMP7 coordinates allergic lung inflammation by activating interleukin 25 while simultaneously inhibiting retinoid-dependent development of regulatory T cells.

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