title: Bronchial Epithelial Cells from Asthmatic Patients Display Less Functional HLA-G Isoform Expression.
abstract: Not all asthmatic patients adequately respond to current available treatments, such as inhaled corticosteroids or omalizumab®. New treatments will aim to target the bronchial epithelium-immune response interaction using different pathways. HLA-G is involved in immunomodulation and may promote epithelial cell differentiation and proliferation. HLA-G protein has several isoforms generated by alternative splicing that might have differential functionalities. HLA-G protein expression and genetic polymorphisms have been reported to be associated with asthma. Our hypothesis is that bronchial epithelium from asthmatic patients displays less functional HLA-G isoforms. HLA-G transcriptional isoforms were quantified by real-time PCR in human bronchial epithelium cells (HBEC) grown in air-liquid interface culture obtained from five healthy controls (HC), seven patients with mild asthma (MA), and seven patients with severe asthma (SA). They were re-differentiated, and IL-13 exposure was used as a proxy for a pro-inflammatory cytokine. HLA-G protein expression was assessed by western blot analysis. HLA-G allele was typed by direct sequencing. Our results showed that both MA and SA display less functional HLA-G isoforms than HC (p< 0.05);in vitroHBEC re-differentiation from SA displays a particular isoform expression profile compared to MA and HC (p= 0.03); HLA-G*01:06 frequency in MA and SA was significantly higher than in the healthy population (p= 0.03 andp< 0.001, respectively); and IL-13 exposure had no impact on HLA-G expression. Our results support that an impaired expression of HLA-G isoforms in asthmatic patients could contribute to the loss of inflammation control and epithelium structural remodeling. Therefore, HLA-G might be an interesting alternative target for asthmatic patients not adequately responding to current drugs.
authors.affiliation: Etablissement Français du Sang Alpes Méditerranée , Marseille , France.
authors.forename: Federico
authors.initials: F
authors.lastname: Carlini
authors.affiliation: Etablissement Français du Sang Alpes Méditerranée, Marseille, France; Aix-Marseille Univ, CNRS, EFS, ADES, "Biologie des Groupes Sanguins", Marseille, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Picard
authors.affiliation: Aix-Marseille Univ, INSERM U1067 CNRS UMR 7333 , Marseille , France.
authors.forename: Céline
authors.initials: C
authors.lastname: Garulli
authors.affiliation: ACOBIOM , Montpellier , France.
authors.forename: David
authors.initials: D
authors.lastname: Piquemal
authors.affiliation: INSERM U491, Génétique Médicale et Développement, Aix-Marseille Université , Marseille , France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Roubertoux
authors.affiliation: Etablissement Français du Sang Alpes Méditerranée, Marseille, France; Aix-Marseille Univ, CNRS, EFS, ADES, "Biologie des Groupes Sanguins", Marseille, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Chiaroni
authors.affiliation: Aix-Marseille Univ, INSERM U1067 CNRS UMR 7333, Marseille, France; Clinique des Bronches, Allergie et Sommeil, AP-HM Hôpital Nord, Marseille, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Chanez
authors.affiliation: Aix-Marseille Univ, INSERM U1067 CNRS UMR 7333 , Marseille , France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Gras
authors.affiliation: Etablissement Français du Sang Alpes Méditerranée, Marseille, France; Aix-Marseille Univ, CNRS, EFS, ADES, "Biologie des Groupes Sanguins", Marseille, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Di Cristofaro
keywords: HLA-G; asthma; epithelium; immunomodulation; isoforms