Mueller, Matthias and Di Padova, Franco E. (2015) IL-1R1-MyD88 axis elicits early papain-induced lung inflammation. Journal of Molecular Cell Biology.

Abstract

Allergic asthma is characterized by a strong Th2 response with inflammatory cell recruitment and structural changes in the lung. Papain is a protease allergen disrupting the airway epithelium triggering a rapid inflammation with eosinophilia mediated by innate lymphoid cell activation (ILC2) and leading to a Th2 immune response. In this study, we focused on the early inflammatory responses to papain. A single intranasal administration of papain (25 μg) resulted in the recruitment of inflammatory cells, including neutrophils and eosinophils as well as a rapid production of IL-1, IL-1β, and IL-33. We showed that papain-induced lung inflammation was abrogated in the absence of MyD88. The lack of IL-1R1 recapitulated the effect of MyD88 deficiency. Eosinophilic response was significantly reduced, whereas neutrophils were markedly increased in ST2 deficient mice. IL-36R signaling was devoid of any effect on the inflammatory response. Using cell-specific MyD88 deficient mice we demonstrated that MyD88 signaling in T cells, epithelial cells, CD11c and myeloid cells did not recapitulate the phenotype of MyD88-/- mice indicating that MyD88 expression is necessary in several of these cells or/and other cell types for the development of papain-induced lung inflammation. In conclusion, IL-1R1 signaling via MyD88 is critical for the early inflammatory response to papain.

Item Type:	Article
Date Deposited:	27 Apr 2016 23:45
Last Modified:	27 Apr 2016 23:45
URI:	https://oak.novartis.com/id/eprint/26934