miRNAs affect the expression of innate and adaptive immunity proteins in celiac disease

Serena Magni, Gaia B uoli Comani, Luca Elli, Samanta Vanessi, Elisa Ballarini, Gabriella Nicolini, Michela Rusconi, Mirco Castoldi, Raffaella Meneveri, Martina U. Muckenthaler, Maria T eresa Bardella, Donatella Barisani

Research output: Contribution to journalArticlepeer-review

Abstract

OBJECTIVES: 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.

Original languageEnglish
Pages (from-to)1662-1674
Number of pages13
JournalAmerican Journal of Gastroenterology
Volume109
Issue number10
DOIs
Publication statusPublished - Oct 1 2014

ASJC Scopus subject areas

  • Medicine(all)

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