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



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.



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).



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.
*Third Department of Internal Medicine, Division of Gastroenterology and Hepatology, Kansai Medical University, Osaka, Japan; †Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Huddinge, Sweden; and ‡Department of Medicine Solna, Karolinska Institutet, Center for Digestive Diseases, Karolinska University Hospital, Stockholm, Sweden.
Yugo
Y
Ando
Luca
L
Mazzurana
Marianne
M
Forkel
Kazuichi
K
Okazaki
Mamiko
M
Aoi
Peter T
PT
Schmidt
Jenny
J
Mjösberg
Francesca
F
Bresso
D000328:Adult; D000368:Aged; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001706:Biopsy; D017252:CD3 Complex / Q000276:immunology; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D003106:Colon / Q000473:pathology; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D016601:RNA-Binding Proteins / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012074:Remission Induction; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; D017252:CD3 Complex; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; C114487:PDCD4 protein, human; D016601:RNA-Binding Proteins