miR-301a promotes intestinal mucosal inflammation through induction of IL-17A and TNF-α in IBD.
MicroRNA (miR)-301a is known to be involved in the tumourigenesis and pathogenesis of several autoimmune diseases, but it remains unclear whether miR-301a is associated with the pathogenesis of IBD.



miR-301a expression was assessed in peripheral blood mononuclear cells (PBMC) and inflamed mucosa of patients with IBD by quantitative real-time-PCR. Peripheral blood CD4+ T cells were transduced with lentivirus-encoding pre-miR-301a (LV-miR-301a) or a reverse complementary sequence of miR-301a (LV-anti-miR-301a), and their differentiation and activation were investigated in vitro. Antisense miR-301a was administered into mice during trinitrobenzene sulphonic acid (TNBS)-induced colitis to determine its role in colitis.



miR-301a expression was significantly upregulated in PBMC and inflamed mucosa of patients with IBD compared with healthy controls. Stimulation with tumour necrosis factor-α (TNF-α) significantly enhanced miR-301a expression in IBD CD4+ T cells, which was markedly reversed by anti-TNF-α mAb (Infliximab) treatment. Transduction of LV-miR-301a into CD4+ T cells from patients with IBD promoted the Th17 cell differentiation and TNF-α production compared with the cells with expression of LV-anti-miR-301a. SNIP1 as a functional target of miR-301a was reduced in miR-301a expression but increased in LV-anti-miR-301a expression. Knockdown of SNIP1 could enhance Th17 cell differentiation. Furthermore, intracolonical administration of antisense miR-301a in TNBS-induced mouse colitis model significantly decreased numbers of interleukin (IL)-17A+cells and amounts of pro-inflammatory cytokines (eg, IL-17A, TNF-α) in inflamed colon.



Our data reveal a novel mechanism in which the elevated miR-301a in PBMC and inflamed mucosa of IBD promotes Th17 cell differentiation through downregulation of SNIP1. Blockade of miR-301a in vivo may serve as a novel therapeutic approach in the treatment of IBD.
Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
Chong
C
He
Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
Yan
Y
Shi
Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
Ruijin
R
Wu
Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
Mingming
M
Sun
Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
Leilei
L
Fang
Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.|Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, Texas, USA.
Wei
W
Wu
Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
Changqin
C
Liu
Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
Maochun
M
Tang
Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
Zhong
Z
Li
Central Laboratory for Medical Research, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
Ping
P
Wang
Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, Texas, USA.|Department of Pathology, The University of Texas Medical Branch, Galveston, Texas, USA.
Yingzi
Y
Cong
Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
Zhanju
Z
Liu
D000818:Animals; D015415:Biomarkers / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D004195:Disease Models, Animal; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000276:immunology; D015212:Inflammatory Bowel Diseases / Q000097:blood / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D020381:Interleukin-17 / Q000097:blood* / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology* / Q000473:pathology; D051379:Mice; D035683:MicroRNAs / Q000097:blood* / Q000276:immunology; D011379:Prognosis; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology*
D015415:Biomarkers; D020381:Interleukin-17; C550735:MIRN301A microRNA, human; D035683:MicroRNAs; D014409:Tumor Necrosis Factor-alpha
IBD BASIC RESEARCH; IMMUNOREGULATION; MUCOSAL IMMUNITY