title: miRNAs affect the expression of innate and adaptive immunity proteins in celiac disease.
abstract: OBJECTIVE
  microRNAs (miRNAs) are short RNAs that regulate gene expression in various processes, including immune response. Altered immune response is a pivotal event in the pathogenesis of celiac disease (CD), and miRNAs could have a role in modulating both innate and adaptive response to gluten in celiac patients.
  
  
  METHODS
  We compared miRNA profiles in duodenal biopsies of controls and CD patients by miRNA array. Differentially expressed miRNAs were validated in controls, Marsh 3A-B, and Marsh 3C patients by quantitative PCR (qPCR). Target gene expression was assessed by qPCR, western blotting, and immunohistochemistry, and the effect of gliadin was evaluated by in vitro stimulation experiments on duodenal biopsies.
  
  
  RESULTS
  Seven miRNAs were identified as significantly downregulated in the duodenum of adult CD patients as compared with controls. qPCR validated the decreased expression of miR-192-5p, miR-31-5p, miR-338-3p, and miR-197, in particular in patients with more severe histological lesions (Marsh 3C). In silico analysis of possible miRNA targets identified several genes involved in innate and adaptive immunity. Among these, chemokine C-X-C motif ligand 2 (CXCL2) and NOD2 showed significantly increased mRNA and protein level in Marsh 3C patients and a significant inverse correlation with the regulatory miR-192-5p. In addition, forkhead box P3 (FOXP3), Run-related transcription factor 1, and interleukin-18 (targets of miR-31-5p, miR-338-3p, and miR-197, respectively) showed upregulation in CD patients. Furthermore, alterations in CXCL2 and NOD2, FOXP3, miR-192-5p, and miR-31-5p expression were triggered by gliadin exposure in CD patients.
  
  
  CONCLUSIONS
  miRNA expression is significantly altered in duodenal mucosa of CD patients, and this alteration can increase the expression of molecules involved in immune response.
authors: Department of Health Sciences, School of Medicine, University of Milano-Bicocca, Monza, Italy.
authors: Serena
authors: S
authors: Magni
authors: Department of Health Sciences, School of Medicine, University of Milano-Bicocca, Monza, Italy.
authors: Gaia
authors: G
authors: Buoli Comani
authors: Center for the Prevention and Diagnosis of Celiac Disease and UOC Gastroenterologia ed Endoscopia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Milan, Italy.
authors: Luca
authors: L
authors: Elli
authors: Department of Health Sciences, School of Medicine, University of Milano-Bicocca, Monza, Italy.
authors: Samanta
authors: S
authors: Vanessi
authors: Experimental Neurology Unit, Department of Surgery and Translational Medicine, School of Medicine, University of Milano-Bicocca, Monza, Italy.
authors: Elisa
authors: E
authors: Ballarini
authors: Experimental Neurology Unit, Department of Surgery and Translational Medicine, School of Medicine, University of Milano-Bicocca, Monza, Italy.
authors: Gabriella
authors: G
authors: Nicolini
authors: Department of Health Sciences, School of Medicine, University of Milano-Bicocca, Monza, Italy.
authors: Michela
authors: M
authors: Rusconi
authors: 1] Department of Pediatric Oncology, Hematology and Immunology, University Hospital of Heidelberg, Heidelberg, Germany [2] Clinic for Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany.
authors: Mirco
authors: M
authors: Castoldi
authors: Department of Health Sciences, School of Medicine, University of Milano-Bicocca, Monza, Italy.
authors: Raffaella
authors: R
authors: Meneveri
authors: Department of Pediatric Oncology, Hematology and Immunology, University Hospital of Heidelberg, Heidelberg, Germany.
authors: Martina U
authors: MU
authors: Muckenthaler
authors: Center for the Prevention and Diagnosis of Celiac Disease and UOC Gastroenterologia ed Endoscopia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Milan, Italy.
authors: Maria Teresa
authors: MT
authors: Bardella
authors: 1] Department of Health Sciences, School of Medicine, University of Milano-Bicocca, Monza, Italy [2] International Research Center for Hepato-Biliary-Pancreatic Diseases-IRCHD, University of Milano-Bicocca, Monza, Italy.
authors: Donatella
authors: D
authors: Barisani
mesh_terms: D056704:Adaptive Immunity / Q000502:physiology*; D000328:Adult; D016022:Case-Control Studies; D002446:Celiac Disease / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D015331:Cohort Studies; D004386:Duodenum / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology*; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D046228:Microarray Analysis; D008875:Middle Aged
chemical_list: C546783:MIRN192 microRNA, human; C546085:MIRN197 microRNA, human; C534612:MIRN31 microRNA, human; C532050:MIRN338 microRNA, human; D035683:MicroRNAs