A pathogenic role for the integrin CD103 in experimental allergic airways disease

Vanessa S. Fear, Siew Ping Lai, Graeme R. Zosky, Kara L. Perks, Shelley Gorman, Fabian Blank, Christophe Von Garnier, Philip A. Stumbles, Deborah H. Strickland

Research output: Contribution to journalArticle

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Abstract

The integrin CD103 is the αE chain of integrin αEβ7 that is important in the maintenance of intraepithelial lymphocytes and recruitment of T cells and dendritic cells (DC) to mucosal surfaces. The role of CD103 in intestinal immune homeostasis has been well described, however, its role in allergic airway inflammation is less well understood. In this study, we used an ovalbumin (OVA)-induced, CD103-knockout (KO) BALB/c mouse model of experimental allergic airways disease (EAAD) to investigate the role of CD103 in disease expression, CD4+ T-cell activation and DC activation and function in airways and lymph nodes. We found reduced airways hyper-responsiveness and eosinophil recruitment to airways after aerosol challenge of CD103 KO compared to wild-type (WT) mice, although CD103 KO mice showed enhanced serum OVA-specific IgE levels. Following aerosol challenge, total numbers of effector and regulatory CD4+ T-cell subsets were significantly increased in the airways of WT but not CD103 KO mice, as well as a lack of DC recruitment into the airways in the absence of CD103. While total airway DC numbers, and their in vivo allergen capture activity, were essentially normal in steady-state CD103 KO mice, migration of allergen-laden airway DC to draining lymph nodes was disrupted in the absence of CD103 at 24 h after aerosol challenge. These data support a role for CD103 in the pathogenesis of EAAD in BALB/c mice through local control of CD4+ T cell and DC subset recruitment to, and migration from, the airway mucosa during induction of allergic inflammation.

Original languageEnglish
Article numbere13021
JournalPhysiological Reports
Volume4
Issue number21
DOIs
Publication statusPublished - 1 Nov 2016

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Integrins
Dendritic Cells
Aerosols
Knockout Mice
Ovalbumin
T-Lymphocytes
Allergens
Respiratory Hypersensitivity
Lymph Nodes
Inflammation
T-Lymphocyte Subsets
Regulatory T-Lymphocytes
Eosinophils
Immunoglobulin E
Mucous Membrane
Homeostasis
Theoretical Models
Cell Count
Maintenance
Lymphocytes

Cite this

Fear, Vanessa S. ; Lai, Siew Ping ; Zosky, Graeme R. ; Perks, Kara L. ; Gorman, Shelley ; Blank, Fabian ; Von Garnier, Christophe ; Stumbles, Philip A. ; Strickland, Deborah H. / A pathogenic role for the integrin CD103 in experimental allergic airways disease. In: Physiological Reports. 2016 ; Vol. 4, No. 21.
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A pathogenic role for the integrin CD103 in experimental allergic airways disease. / Fear, Vanessa S.; Lai, Siew Ping; Zosky, Graeme R.; Perks, Kara L.; Gorman, Shelley; Blank, Fabian; Von Garnier, Christophe; Stumbles, Philip A.; Strickland, Deborah H.

In: Physiological Reports, Vol. 4, No. 21, e13021, 01.11.2016.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A pathogenic role for the integrin CD103 in experimental allergic airways disease

AU - Fear, Vanessa S.

AU - Lai, Siew Ping

AU - Zosky, Graeme R.

AU - Perks, Kara L.

AU - Gorman, Shelley

AU - Blank, Fabian

AU - Von Garnier, Christophe

AU - Stumbles, Philip A.

AU - Strickland, Deborah H.

PY - 2016/11/1

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N2 - The integrin CD103 is the αE chain of integrin αEβ7 that is important in the maintenance of intraepithelial lymphocytes and recruitment of T cells and dendritic cells (DC) to mucosal surfaces. The role of CD103 in intestinal immune homeostasis has been well described, however, its role in allergic airway inflammation is less well understood. In this study, we used an ovalbumin (OVA)-induced, CD103-knockout (KO) BALB/c mouse model of experimental allergic airways disease (EAAD) to investigate the role of CD103 in disease expression, CD4+ T-cell activation and DC activation and function in airways and lymph nodes. We found reduced airways hyper-responsiveness and eosinophil recruitment to airways after aerosol challenge of CD103 KO compared to wild-type (WT) mice, although CD103 KO mice showed enhanced serum OVA-specific IgE levels. Following aerosol challenge, total numbers of effector and regulatory CD4+ T-cell subsets were significantly increased in the airways of WT but not CD103 KO mice, as well as a lack of DC recruitment into the airways in the absence of CD103. While total airway DC numbers, and their in vivo allergen capture activity, were essentially normal in steady-state CD103 KO mice, migration of allergen-laden airway DC to draining lymph nodes was disrupted in the absence of CD103 at 24 h after aerosol challenge. These data support a role for CD103 in the pathogenesis of EAAD in BALB/c mice through local control of CD4+ T cell and DC subset recruitment to, and migration from, the airway mucosa during induction of allergic inflammation.

AB - The integrin CD103 is the αE chain of integrin αEβ7 that is important in the maintenance of intraepithelial lymphocytes and recruitment of T cells and dendritic cells (DC) to mucosal surfaces. The role of CD103 in intestinal immune homeostasis has been well described, however, its role in allergic airway inflammation is less well understood. In this study, we used an ovalbumin (OVA)-induced, CD103-knockout (KO) BALB/c mouse model of experimental allergic airways disease (EAAD) to investigate the role of CD103 in disease expression, CD4+ T-cell activation and DC activation and function in airways and lymph nodes. We found reduced airways hyper-responsiveness and eosinophil recruitment to airways after aerosol challenge of CD103 KO compared to wild-type (WT) mice, although CD103 KO mice showed enhanced serum OVA-specific IgE levels. Following aerosol challenge, total numbers of effector and regulatory CD4+ T-cell subsets were significantly increased in the airways of WT but not CD103 KO mice, as well as a lack of DC recruitment into the airways in the absence of CD103. While total airway DC numbers, and their in vivo allergen capture activity, were essentially normal in steady-state CD103 KO mice, migration of allergen-laden airway DC to draining lymph nodes was disrupted in the absence of CD103 at 24 h after aerosol challenge. These data support a role for CD103 in the pathogenesis of EAAD in BALB/c mice through local control of CD4+ T cell and DC subset recruitment to, and migration from, the airway mucosa during induction of allergic inflammation.

KW - Allergy

KW - Asthma

KW - CD103

KW - CD4 T cell

KW - Dendritic cell

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U2 - 10.14814/phy2.13021

DO - 10.14814/phy2.13021

M3 - Article

VL - 4

JO - Physiological Reports

JF - Physiological Reports

SN - 2051-817X

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