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

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• 作者：Matthew J. Gold ; PhD^a ; ^&lowast ; ; Michael R. Hughes ; PhD^a ; ^&lowast ; ; Frann Antignano ; PhD^a ; Jeremy A. Hirota ; PhD^b ; Colby Zaph ; PhD^a ; ^c ; ^d ; Kelly M. McNagny ; PhD^a ; ^{kelly@brc.ubc.ca" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Allergy ; asthma ; dendritic cell ; house dust mite ; IgE ; TH2
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2015
• 出版时间：September 2015
• 年：2015
• 卷：136
• 期：3
• 页码：725-736.e2
• 全文大小：5775 K

文摘

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.

2">Objective

15">We hypothesized that lineage-specific deletion of Ship1 expression in cells known to be crucial for adaptive T_H2 responses would uncover distinct roles that could either positively or negatively regulate susceptibility to allergic airway inflammation (AAI).

Methods

20">Ship1 expression was deleted in B cells, T cells, or dendritic cells (DCs), and the resulting Ship1^{螖B cell}, Ship1^{螖T cell}, Ship1^螖DC, or Ship1^F/F (wild-type) control mice were evaluated in a model of house dust mite (HDM)–induced AAI.

Results

25">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 T_H2 immune response toward a T_H1 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 T_H2 response and protects animals from HDM-induced AAI.