RESUMO
OBJECTIVE: The aim was to investigate the mucosal activation of a broad range of genes associated with the T-helper 17 cell (Th17) signaling pathway in children at different stages of celiac disease (CD), including children with increased risk for CD and children with untreated and gluten-free diet (GFD)-treated CD. MATERIAL AND METHODS: Small intestinal biopsies were taken from children with untreated and GFD-treated CD, transglutaminase antibody (TGA)-positive children with potential CD, and reference children. Real-time polymerase chain reaction (PCR) arrays were used to study the gene expression pattern of Th17-related genes, and quantitative PCR was used to study the interleukin (IL)-17A expression. RESULTS: The mucosal expression of CD8A was elevated at all stages of CD. Children with untreated CD had diminished levels of IL-17RE, IL-23R, RORc, STAT6, CCL22, NFATC2, IL-18, CD4, CD247, and matrix metalloproteinase (MMP)9 but had elevated levels of MMP3, IL-17, interferon-γ (IFN-γ) and CD8A, compared to references. The majority of the aforementioned genes, being differentially expressed in untreated CD, displayed similar expression in GFD-treated children and references. Children with untreated and GFD-treated CD had elevated expression of IFN-γ but had reduced expression of CD247. Interestingly, children with potential CD displayed reduced FOXP3, IL-21, and IL-17A levels. CONCLUSION: Mucosal upregulation of Th17 immunity occurs at the late stage of disease and is downregulated with dietary treatment, thus indicating that IL-17 immunity is not a fundamental feature of CD as Th1 immunity, which is not fully downregulated by GFD.
Assuntos
Antígenos CD/genética , Doença Celíaca/genética , Expressão Gênica , Peptídeos e Proteínas de Sinalização Intercelular/genética , Receptores de Interleucina/genética , Transdução de Sinais/genética , Células Th17/metabolismo , Fatores de Transcrição/genética , Adolescente , Anticorpos/sangue , Estudos de Casos e Controles , Doença Celíaca/dietoterapia , Doença Celíaca/imunologia , Criança , Pré-Escolar , Enterite/genética , Enterite/imunologia , Feminino , Proteínas de Ligação ao GTP , Humanos , Lactente , Mucosa Intestinal/imunologia , Mucosa Intestinal/patologia , Masculino , Metaloproteinase 3 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Proteína 2 Glutamina gama-Glutamiltransferase , Transglutaminases/imunologiaRESUMO
The global expression of immune response genes in infants after vaccination and their role in asthma and allergy is not clearly understood. Pharmacogenomics is ideally suited to study the involved cellular responses, since the expression of thousands of genes can be assessed simultaneously. Here, array technology was used to assess the expression kinetics of immune response genes with association to asthma and allergy in peripheral blood mononuclear cells (PBMC) of five healthy infants after vaccination with Infanrix-Polio+Hib. At 12h after in vitro re-stimulation of the PBMC with pertussis toxin (PT) antigen, 14 immune response pathways, 33 allergy-related and 66 asthma-related genes were found activated.