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

Sangeeta Goswami, Pornpimon Angkasekwinai, Ming Shan, Kendra J. Greenlee, Wade T. Barranco, Sumanth Polikepahad, Alexander Seryshev, Li Zhen Song, David Redding, Bhupinder Singh, Sanjiv Sur, Prescott Woodruff, Chen Dong, David B. Corry, Farrah Kheradmand

Research output: Contribution to journalArticlepeer-review

82 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)496-503
Number of pages8
JournalNature Immunology
Volume10
Issue number5
DOIs
StatePublished - 2009

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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