title: Cbl-b Deficiency in Mice Results in Exacerbation of Acute and Chronic Stages of Allergic Asthma.
abstract: Mice sensitized to ovalbumin (OVA) develop allergic airway disease (AAD) with short-term daily OVA aerosol challenge; inflammation resolves with long-term OVA aerosol exposure, resulting in local inhalational tolerance (LIT). Cbl-b is an E3 ubiquitin ligase involved with CD28 signaling; Cbl-b(-/-) effector T cells are resistant to regulatory T cell-mediated suppression in vitro and in vivo. The present study utilized Cbl-b(-/-) mice to investigate the role of Cbl-b in the development of AAD and LIT. Cbl-b(-/-) mice exhibited increased airway inflammation during AAD, which failed to resolve with long-term OVA aerosol exposure. Exacerbation of inflammation in Cbl-b(-/-) mice correlated with increased proinflammatory cytokine levels and expansion of effector T cells in the BAL during AAD, but did not result in either a modulation of lymphocyte subsets in systemic tissues or in OVA-specific IgE in serum. These results implicate a role for Cbl-b in the resolution of allergic airway inflammation.
authors.affiliation: Department of Pathology, University of Michigan , Ann Arbor, MI , USA.
authors.forename: William F
authors.initials: WF
authors.lastname: Carson
authors.affiliation: Department of Immunology, University of Connecticut Health Center , Farmington, CT , USA.
authors.forename: Linda A
authors.initials: LA
authors.lastname: Guernsey
authors.affiliation: Department of Immunology, University of Connecticut Health Center , Farmington, CT , USA.
authors.forename: Anurag
authors.initials: A
authors.lastname: Singh
authors.affiliation: Department of Immunology, University of Connecticut Health Center , Farmington, CT , USA.
authors.forename: Eric R
authors.initials: ER
authors.lastname: Secor
authors.affiliation: Department of Pediatrics, University of Connecticut Health Center , Farmington, CT , USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Wohlfert
authors.affiliation: Department of Immunology, University of Connecticut Health Center , Farmington, CT , USA.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Clark
authors.affiliation: Department of Microbiology and Immunology, University at Buffalo , Buffalo, NY , USA.
authors.forename: Craig M
authors.initials: CM
authors.lastname: Schramm
authors.affiliation: Department of Pathology, University of Michigan , Ann Arbor, MI , USA.
authors.forename: Steven L
authors.initials: SL
authors.lastname: Kunkel
authors.affiliation: Department of Immunology, University of Connecticut Health Center , Farmington, CT , USA.
authors.forename: Roger S
authors.initials: RS
authors.lastname: Thrall
keywords: CD4+ T cells; Cbl-b; allergic airway disease; inflammation; tolerance