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 Corry, Farrah Kheradmand

    Research output: Contribution to journalArticlepeer-review

    97 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

    Fingerprint

    Dive into the research topics of 'Divergent functions for airway epithelial matrix metalloproteinase 7 and retinoic acid in experimental asthma'. Together they form a unique fingerprint.

    Cite this