title: A pathogenic role for the integrin CD103 in experimental allergic airways disease.
abstract: The integrin CD103 is the αEchain of integrin αEβ7that 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.
authors.affiliation: Telethon Kids Institute, Perth, Australia.
authors.forename: Vanessa S
authors.initials: VS
authors.lastname: Fear
authors.affiliation: Telethon Kids Institute, Perth, Australia.
authors.forename: Siew Ping
authors.initials: SP
authors.lastname: Lai
authors.affiliation: Telethon Kids Institute, Perth, Australia.
authors.forename: Graeme R
authors.initials: GR
authors.lastname: Zosky
authors.affiliation: Telethon Kids Institute, Perth, Australia.
authors.forename: Kara L
authors.initials: KL
authors.lastname: Perks
authors.affiliation: Telethon Kids Institute, Perth, Australia.
authors.forename: Shelley
authors.initials: S
authors.lastname: Gorman
authors.affiliation: Department of Clinical Research, University of Bern, Bern, Switzerland.
authors.forename: Fabian
authors.initials: F
authors.lastname: Blank
authors.affiliation: Department of Clinical Research, University of Bern, Bern, Switzerland.
authors.forename: Christophe
authors.initials: C
authors.lastname: von Garnier
authors.affiliation: Telethon Kids Institute, Perth, Australia.|School of Veterinary and Life Sciences, Murdoch University, Perth, Australia.|School of Paediatrics and Child Health, University of Western Australia, Perth, Australia.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Stumbles
authors.affiliation: Telethon Kids Institute, Perth, Australia Deb.Strickland@telethonkids.org.au.|School of Paediatrics and Child Health, University of Western Australia, Perth, Australia.
authors.forename: Deborah H
authors.initials: DH
authors.lastname: Strickland
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D001249:Asthma / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000502:physiology; D005260:Female; D006967:Hypersensitivity / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology*; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism; D039001:Integrin alpha Chains / Q000378:metabolism*; D016023:Integrins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D023421:Models, Animal; D010047:Ovalbumin / Q000097:blood / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D039001:Integrin alpha Chains; D016023:Integrins; C091367:alpha E integrins; C070709:integrin alphaEbeta7; D010047:Ovalbumin
keywords: Allergy; CD103; CD4 T cell; asthma; dendritic cell