Mechanisms of allergy and clinical immunologyPeriostin is required for maximal airways inflammation and hyperresponsiveness in mice

BackgroundPeriostin, a secreted extracellular matrix protein, has been localized to deposits of subepithelial fibrosis in asthmatic patients, and periostin levels have been linked to increases in IL-13.ObjectiveWe hypothesized that periostin is required for airway inflammatory responses to a physiologic aeroallergen, house dust mite (HDM).MethodsWe studied F4-F6 B6;129-Postntm1Jmol/J wild-type (Postn+/+) and null (Postn−/−) mice, as well as C57BL/6 mice treated with either IgM or OC-20 periostin neutralizing antibody. Mice were exposed to 5 doses of HDM intranasally over a 16-day period.ResultsHDM increased airways responsiveness in Postn+/+ but not Postn−/− mice. In addition, HDM-treated C57BL/6 mice injected with OC-20 had lower airways responsiveness than HDM-treated mice injected with IgM. Compared with Postn+/+ mice, Postn−/− mice showed decreases in HDM-induced inflammation and mucous metaplasia, as well as reduced IL-4, IL-25, CD68, Gob5, and periostin mRNA expression. OC-20 antibody produced similar results. HDM exposure increased periostin expression in the airway epithelium, subepithelium, smooth muscle and inflammatory cells. OC-20 blocked the HDM-induced IgE response, and T cells incubated with dendritic cells (DCs) from Postn−/− mice or treated with OC-20 showed deficient DNA synthesis and IL-13 responses compared with T cells incubated with wild-type DCs. Finally, adoptive transfer of bone marrow-derived DCs from Postn+/+ mice was sufficient to promote allergic responses in F6 Postn−/− littermates.ConclusionsIn mice, periostin is required for maximal airways hyperresponsiveness and inflammation after HDM sensitization and challenge. Periostin is required for maximal HDM-induced T-cell responses.