Downregulation of MicroRNA-21 in Colonic CD3+ T Cells in UC Remission.

Abstract

BACKGROUND:

In active inflammatory bowel disease (IBD), microRNA expression profiling consistently features disease-specific signatures, and microRNA-21 (miR-21) has been shown to be upregulated in the inflamed colon of patients with active ulcerative colitis (UC). However, the cellular sources of miR-21 expression in IBD tissues have not yet been identified. We sought to determine the expression levels of miR-21 and one of its downstream target genes, programmed cell death 4 (PDCD4), in CD3 T cells isolated from the colonic mucosa of patients with active IBD, inactive IBD, and non-IBD controls.

METHODS:

Colonic biopsies were treated with collagenase V. CD3 T cells were isolated using MACS CD3 positive selection. Total RNA was converted to cDNA. Real-time PCR reactions were performed with PCR primers for miR-21, SNORD95, PDCD4, and GAPDH.

RESULTS:

The expression of miR-21 was statistically significantly downregulated in CD3 T cells from patients with UC in remission as compared to active disease (P = 0.0193). miR-21 negatively regulates PDCD4 expression. As predicted, the mRNA level of PCDC4 in CD3 T cells was upregulated in UC and Crohn's disease in remission as compared to active disease (UC active versus UC remission: P = 0.0008, Crohn's disease active versus Crohn's disease remission: P = 0.0215) and in patients with UC in remission as compared to healthy controls (P = 0.0226).

CONCLUSIONS:

Although miR-21 expression is downregulated, PDCD4 is upregulated in CD3 T cells during the remission phase of UC. Our results indicate that miR-21 and related pathways in colonic T cells may play a role in limiting pathogenic T-cell responses and may constitute future target candidates to induce remission in UC.

• Authors: Yugo Ando, Luca Mazzurana, Marianne Forkel, Kazuichi Okazaki, Mamiko Aoi, Peter T Schmidt, Jenny Mjösberg, Francesca Bresso
• Journal: Inflammatory bowel diseases (Inflamm Bowel Dis) Vol. 22 Issue 12 Pg. 2788-2793 (12 2016) ISSN: 1536-4844 [Electronic] England
• PMID: 27824649 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apoptosis Regulatory Proteins
• CD3 Complex
• MIRN21 microRNA, human
• MicroRNAs
• PDCD4 protein, human
• RNA-Binding Proteins

Topics

• Adult
• Aged
• Apoptosis Regulatory Proteins (metabolism)
• Biopsy
• CD3 Complex (immunology)
• Case-Control Studies
• Colitis, Ulcerative (genetics, immunology, pathology)
• Colon (pathology)
• Down-Regulation
• Female
• Humans
• Intestinal Mucosa (immunology, metabolism, pathology)
• Male
• MicroRNAs (metabolism)
• Middle Aged
• RNA-Binding Proteins (metabolism)
• Real-Time Polymerase Chain Reaction
• Remission Induction
• T-Lymphocyte Subsets (immunology, metabolism)