Abstract
Abstract The innate immune response of airway epithelial cells to aeroallergen likely initiates the development of T cell responses that are central to allergic inflammation. Although proteolytically active allergens induce the expression of interleukin (IL)-25/IL-17E, we show that epithelial matrix metalloproteinase 7 (MMP7) is expressed in human asthma, and is required for maximal activity of this cytokine in promoting T helper type 2 cell differentiation. Allergen-challenged MMP7-/- mice showed reduced airway hyperreactivity, allergic inflammatory cytokine, and increased expression of retinal dehydrogenase (RALDH)-1. Inhibition of RALDH-1 restored the asthma phenotype in MMP7-/- mice and inhibited lung T regulatory cell responses while exogenous administration of retinoic acid attenuated the asthma phenotype. Thus, MMP7 coordinates allergic lung inflammation by activating IL-25 while simultaneously inhibiting retinoid-dependent T regulatory cell development.
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