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