title: Divergent functions for airway epithelial matrix metalloproteinase 7 and retinoic acid in experimental asthma.
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.
authors.affiliation: Department of Immunology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Goswami
authors.forename: Pornpimon
authors.initials: P
authors.lastname: Angkasekwinai
authors.forename: Ming
authors.initials: M
authors.lastname: Shan
authors.forename: Kendra J
authors.initials: KJ
authors.lastname: Greenlee
authors.forename: Wade T
authors.initials: WT
authors.lastname: Barranco
authors.forename: Sumanth
authors.initials: S
authors.lastname: Polikepahad
authors.forename: Alexander
authors.initials: A
authors.lastname: Seryshev
authors.forename: Li-zhen
authors.initials: LZ
authors.lastname: Song
authors.forename: David
authors.initials: D
authors.lastname: Redding
authors.forename: Bhupinder
authors.initials: B
authors.lastname: Singh
authors.forename: Sanjiv
authors.initials: S
authors.lastname: Sur
authors.forename: Prescott
authors.initials: P
authors.lastname: Woodruff
authors.forename: Chen
authors.initials: C
authors.lastname: Dong
authors.forename: David B
authors.initials: DB
authors.lastname: Corry
authors.forename: Farrah
authors.initials: F
authors.lastname: Kheradmand