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

Abstract

BACKGROUND:

Inpp5d (Src homology 2 domain-containing inositol-5-phosphatase [Ship1])-deficient mice experience spontaneous airway inflammation and have enhanced sensitivity to allergen-induced airway inflammation.

OBJECTIVE:

We 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).

METHODS:

Ship1 expression was deleted in B cells, T cells, or dendritic cells (DCs), and the resulting Ship1(ΔB cell), Ship1(ΔT cell), Ship1(ΔDC), or Ship1(F/F) (wild-type) control mice were evaluated in a model of house dust mite (HDM)-induced AAI.

RESULTS:

Unlike 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.

CONCLUSIONS:

Although 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.

• Authors: Matthew J Gold, Michael R Hughes, Frann Antignano, Jeremy A Hirota, Colby Zaph, Kelly M McNagny
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 136 Issue 3 Pg. 725-736.e2 (Sep 2015) ISSN: 1097-6825 [Electronic] United States
• PMID: 25746967 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Chemical References

• Allergens
• Antigens, Dermatophagoides
• Phosphoric Monoester Hydrolases
• Inositol Polyphosphate 5-Phosphatases
• Inpp5d protein, mouse
• Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases

Topics

• Adaptive Immunity
• Allergens (administration & dosage, immunology)
• Animals
• Antigens, Dermatophagoides (administration & dosage, immunology)
• B-Lymphocytes (immunology, pathology)
• Bronchial Hyperreactivity (chemically induced, genetics, immunology, pathology)
• Cell Lineage (genetics, immunology)
• Dendritic Cells (immunology, pathology)
• Gene Expression
• Inositol Polyphosphate 5-Phosphatases
• Mice
• Mice, Knockout
• Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases
• Phosphoric Monoester Hydrolases (deficiency, genetics, immunology)
• Pneumonia (chemically induced, genetics, immunology, pathology)
• Pyroglyphidae (chemistry)
• T-Lymphocytes (immunology, pathology)
• Th1-Th2 Balance