Format

Send to

Choose Destination
Front Immunol. 2017 Jan 23;8:6. doi: 10.3389/fimmu.2017.00006. eCollection 2017.

Bronchial Epithelial Cells from Asthmatic Patients Display Less Functional HLA-G Isoform Expression.

Author information

1
Etablissement Français du Sang Alpes Méditerranée , Marseille , France.
2
Etablissement Français du Sang Alpes Méditerranée, Marseille, France; Aix-Marseille Univ, CNRS, EFS, ADES, "Biologie des Groupes Sanguins", Marseille, France.
3
Aix-Marseille Univ, INSERM U1067 CNRS UMR 7333 , Marseille , France.
4
ACOBIOM , Montpellier , France.
5
INSERM U491, Génétique Médicale et Développement, Aix-Marseille Université , Marseille , France.
6
Aix-Marseille Univ, INSERM U1067 CNRS UMR 7333, Marseille, France; Clinique des Bronches, Allergie et Sommeil, AP-HM Hôpital Nord, Marseille, France.

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 vitro HBEC 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 and p < 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.

KEYWORDS:

HLA-G; asthma; epithelium; immunomodulation; isoforms

Supplemental Content

Full text links

Icon for Frontiers Media SA Icon for PubMed Central
Loading ...
Support Center