Effect of Gliadin Stimulation on HLA-DQ2.5 Gene Expression in Macrophages from Adult Celiac Disease Patients
Federica Farina,
Laura Pisapia,
Mariavittoria Laezza,
Gloria Serena,
Antonio Rispo,
Simona Ricciolino,
Carmen Gianfrani,
Alessio Fasano,
Giovanna Del Pozzo
Affiliations
Federica Farina
Institute of Genetics and Biophysics “A. Buzzati-Traverso”, Italian National Council of Research (CNR), 80131 Naples, Italy
Laura Pisapia
Institute of Genetics and Biophysics “A. Buzzati-Traverso”, Italian National Council of Research (CNR), 80131 Naples, Italy
Mariavittoria Laezza
Institute of Genetics and Biophysics “A. Buzzati-Traverso”, Italian National Council of Research (CNR), 80131 Naples, Italy
Gloria Serena
Division of Pediatric Gastroenterology and Nutrition, Center for Celiac Research, Mucosal Immunology and Biology Research Center, Harvard Medical School, Massachusetts General Hospital, Boston, MA 02114, USA
Antonio Rispo
Gastroenterology, Department of Clinical Medicine and Surgery, School of Medicine Federico II of Naples, 80131 Naples, Italy
Simona Ricciolino
Gastroenterology, Department of Clinical Medicine and Surgery, School of Medicine Federico II of Naples, 80131 Naples, Italy
Carmen Gianfrani
Institute of Biochemistry and Cell Biology, Italian National Council of Research (CNR), 80131 Naples, Italy
Alessio Fasano
Division of Pediatric Gastroenterology and Nutrition, Center for Celiac Research, Mucosal Immunology and Biology Research Center, Harvard Medical School, Massachusetts General Hospital, Boston, MA 02114, USA
Giovanna Del Pozzo
Institute of Genetics and Biophysics “A. Buzzati-Traverso”, Italian National Council of Research (CNR), 80131 Naples, Italy
Macrophages play an important role in the pathogenesis of celiac disease (CD) because they are involved in both inflammatory reaction and antigen presentation. We analyzed the expression of CD-associated HLA-DQ2.5 risk alleles on macrophages isolated by two cohorts of adult patients, from the U.S. and Italy, at different stages of disease and with different genotypes. After isolating and differentiating macrophages from PBMC, we assessed the HLA genotype and quantified the HLA-DQ2.5 mRNAs by qPCR, before and after gliadin stimulation. The results confirmed the differences in expression between DQA1*05:01 and DQB1*02:01 predisposing alleles and the non-CD associated alleles, as previously shown on other types of APCs. The gliadin challenge confirmed the differentiation of macrophages toward a proinflammatory phenotype, but above all, it triggered an increase of DQA1*05:01 mRNA, as well as a decrease of the DQB1*02:01 transcript. Furthermore, we observed a decrease in the DRB1 genes expression and a downregulation of the CIITA transactivator. In conclusion, our findings provide new evidences on the non-coordinated regulation of celiac disease DQ2.5 risk genes and support the hypothesis that gliadin could interfere in the three-dimensional arrangement of chromatin at the HLA locus.
