Trefoil factor 2 rapidly induces interleukin 33 to promote type 2 immunity during allergic asthma and hookworm infection

Marsha Wills-Karp, Reena Rani, Krista Dienger, Ian Lewkowich, James G. Fox, Charles Perkins, Lauren Lewis, Fred D. Finkelman, Dirk E. Smith, Paul J. Bryce, Evelyn A. Kurt-Jones, Timothy C. Wang, Umasundari Sivaprasad, Gurjit K. Hershey, De'Broski R. Herbert

Research output: Contribution to journalArticlepeer-review

146 Scopus citations

Abstract

The molecular mechanisms that drive mucosal T helper type 2 (T H2) responses against parasitic helminths and allergens remain unclear. In this study, we demonstrate in mice that TFF2 (trefoil factor 2), an epithelial cell-derived repair molecule, is needed for the control of lung injury caused by the hookworm parasite Nippostrongylus brasiliensis and for type 2 immunity after infection. TFF2 is also necessary for the rapid production of IL-33, a T H2-promoting cytokine, by lung epithelia, alveolar macrophages, and inflammatory dendritic cells in infected mice. TFF2 also increases the severity of allergic lung disease caused by house dust mite antigens or IL-13. Moreover, TFF2 messenger RNA expression is significantly increased in nasal mucosal brushings during asthma exacerbations in children. These experiments extend the biological functions of TFF2 from tissue repair to the initiation and maintenance of mucosal T H2 responses.

Original languageEnglish (US)
Pages (from-to)607-622
Number of pages16
JournalJournal of Experimental Medicine
Volume209
Issue number3
DOIs
StatePublished - Mar 12 2012
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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