Periostin is required for maximal airways inflammation and hyperresponsiveness in mice

J. Kelley Bentley, Qiang Chen, Jun Young Hong, Antonia P. Popova, Jing Lei, Bethany B. Moore, Marc B. Hershenson

Research output: Contribution to journalArticlepeer-review

58 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1433-1442
Number of pages10
JournalJournal of Allergy and Clinical Immunology
Volume134
Issue number6
DOIs
Publication statusPublished - 2014 Dec 1

Bibliographical note

Funding 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.).

Funding Information:
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.

Publisher Copyright:
© 2014 American Academy of Allergy, Asthma & Immunology.

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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