title: Functional defects of CD46-induced regulatory T cells to suppress airway inflammation in mite allergic asthma.
abstract: Defective recruitment of regulatory T cells (Treg) function to the airway is important in the pathogenesis of allergic asthma. Complement regulatory protein (CD46) is a newly defined costimulatory molecule for Treg activation, which together with IL-10/granzyme B production may aid in suppressing asthmatic inflammation. This study examines chemotaxis and adhesion molecule expression on CD3/CD46-activated CD4(+) T cells (Tregs) from patients with and without asthma to suppress mite allergen-induced respiratory epithelial cells inflammation and to elucidate the mechanism of CD46-mediated Treg activation. Diminished IL-10/granzyme B and CCR4 expression from CD3/CD46-activated Tregs appeared in asthmatic subjects. CD3/CD46-activated Tregs from asthma patients co-cultured with BEAS-2B cells suppressed Dermatophagoides pteronyssinus 2 induced nuclear factor-κB/p65 by cell contact inhibition. Decreased interaction of CD3/CD46-mediated Tregs and BEAS-2B cells from asthmatics was associated with downregulated phosphorylation of protein kinase B (AKT) expression. Results provide the first evidence that decreased interaction between CD46-mediated Tregs and lung epithelial cells with less IL-10/granzyme B production may cause airway inflammation in allergic asthma.
authors: Department of Pediatrics, Changhua Christian Hospital, Changhua, Taiwan.
authors: Yi-Giien
authors: YG
authors: Tsai
authors: Dau-Ming
authors: DM
authors: Niu
authors: Kuender D
authors: KD
authors: Yang
authors: Chih-Hsing
authors: CH
authors: Hung
authors: Ya-Ju
authors: YJ
authors: Yeh
authors: Chia-Ying
authors: CY
authors: Lee
authors: Ching-Yuang
authors: CY
authors: Lin
mesh_terms: D000293:Adolescent; D000818:Animals; D001249:Asthma / Q000276:immunology*; D001483:Base Sequence; D001991:Bronchitis / Q000276:immunology*; D002448:Cell Adhesion; D002465:Cell Movement; D002648:Child; D017931:DNA Primers; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D008297:Male; D051916:Membrane Cofactor Protein / Q000276:immunology*; D008925:Mites / Q000276:immunology*; D016328:NF-kappa B / Q000378:metabolism; D016133:Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D017931:DNA Primers; D051916:Membrane Cofactor Protein; D016328:NF-kappa B