Background Periostin, 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. Objective We 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.
Results HDM 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.
Conclusions In 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.
Bibliographical noteFunding Information:
Supported by the Michigan Institute for Clinical and Health Research / National Institutes of Health UL1TR000433 (to J.K.B.), HL115618 (to B.B.M), and HL079339 (to M.B.H.).
Disclosure of potential conflict of interest: M. B. Hershenson's institution has received funding from the National Institutes of Health , as has the institution of B. B. Moore J. K. Bentley's institution has received funding from the Michigan Institute for Clinical & Health Research (MICHR). M. B. Hershenson has also received consultancy fees from Boehringer-Ingelheim and Almirall . The rest of the authors declare that they have no relevant conflicts of interest.
© 2014 American Academy of Allergy, Asthma & Immunology.
All Science Journal Classification (ASJC) codes
- Immunology and Allergy