Lineage-specific regulation of allergic airway inflammation by the lipid phosphatase Src homology 2 domain-containing inositol 5-phosphatase (SHIP-1)

Matthew J. Gold, Michael R. Hughes, Frann Antignano, Jeremy A. Hirota, Colby Zaph, Kelly M. McNagny

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9 Citations (Scopus)


BackgroundInpp5d (Src homology 2 domain–containing inositol-5-phosphatase [Ship1])–deficient mice experience spontaneous airway inflammation and have enhanced sensitivity to allergen-induced airway inflammation.ObjectiveWe hypothesized that lineage-specific deletion of Ship1 expression in cells known to be crucial for adaptive TH2 responses would uncover distinct roles that could either positively or negatively regulate susceptibility to allergic airway inflammation (AAI).MethodsShip1 expression was deleted in B cells, T cells, or dendritic cells (DCs), and the resulting Ship1ΔB cell, Ship1ΔT cell, Ship1ΔDC, or Ship1F/F (wild-type) control mice were evaluated in a model of house dust mite (HDM)–induced AAI.ResultsUnlike germline panhematopoietic Ship1 deletion, deletion of Ship1 selectively in either the B-cell, T-cell, or DC lineages did not result in spontaneous airway inflammation. Strikingly, although loss of Ship1 in the B-cell lineage did not affect HDM-induced AAI, loss of Ship1 in either of the T-cell or DC lineages protected mice from AAI by skewing the typical TH2 immune response toward a TH1 response.ConclusionsAlthough panhematopoietic deletion of Ship1 leads to spontaneous lung inflammation, selective deletion of Ship1 in T cells or DCs impairs the formation of an adaptive TH2 response and protects animals from HDM-induced AAI.
Original languageEnglish
Pages (from-to)725-736
Number of pages12
JournalJournal of Allergy and Clinical Immunology
Issue number3
Publication statusPublished - Sep 2015


  • allergy
  • asthma
  • dendritic cell
  • house dust mite
  • IgE
  • TH2

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