title: miR-155 deficiency protects mice from experimental colitis by reducing T helper type 1/type 17 responses.
abstract: Inflammatory bowel disease (IBD), a chronic intestinal inflammatory condition that affects millions of people worldwide, results in high morbidity and exorbitant health-care costs. The critical features of both innate and adaptive immunity are to control inflammation and dysfunction in this equilibrium is believed to be the reason for the development of IBD. miR-155, a microRNA, is up-regulated in various inflammatory disease states, including IBD, and is a positive regulator of T-cell responses. To date, no reports have defined a function for miR-155 with regard to cellular responses in IBD. Using an acute experimental colitis model, we found that miR-155(-/-) mice, as compared to wild-type control mice, have decreased clinical scores, a reversal of colitis-associated pathogenesis, and reduced systemic and mucosal inflammatory cytokines. The increased frequency of CD4+ lymphocytes in the spleen and lamina propria with dextran sodium sulphate induction was decreased in miR-155(-/-) mice. Similarly, miR-155 deficiency abrogated the increased numbers of interferon-γ expressing CD4+ T cells typically observed in wild-type mice in this model. The frequency of systemic and mucosal T helper type 17-, CCR9-expressing CD4+ T cells was also reduced in miR-155(-/-) mice compared with control mice. These findings strongly support a role for miR-155 in facilitating pro-inflammatory cellular responses in this model of IBD. Loss of miR-155 also results in decreases in T helper type 1/type 17, CD11b+) and CD11c+ cells, which correlated with reduced clinical scores and severity of disease. miR-155 may serve as a potential therapeutic target for the treatment of IBD.
authors.affiliation: Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC, USA.
authors.forename: Udai P
authors.initials: UP
authors.lastname: Singh
authors.forename: Angela E
authors.initials: AE
authors.lastname: Murphy
authors.forename: Reilly T
authors.initials: RT
authors.lastname: Enos
authors.forename: Haidar A
authors.initials: HA
authors.lastname: Shamran
authors.forename: Narendra P
authors.initials: NP
authors.lastname: Singh
authors.forename: Honbing
authors.initials: H
authors.lastname: Guan
authors.forename: Venkatesh L
authors.initials: VL
authors.lastname: Hegde
authors.forename: Daping
authors.initials: D
authors.lastname: Fan
authors.forename: Robert L
authors.initials: RL
authors.lastname: Price
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Taub
authors.forename: Manoj K
authors.initials: MK
authors.lastname: Mishra
authors.forename: Mitzi
authors.initials: M
authors.lastname: Nagarkatti
authors.forename: Prakash S
authors.initials: PS
authors.lastname: Nagarkatti
mesh_terms: D000818:Animals; D001835:Body Weight; D039481:CD11b Antigen / Q000378:metabolism; D039521:CD11c Antigen / Q000378:metabolism; D003092:Colitis / Q000097:blood / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000097:blood; D016264:Dextran Sulfate / Q000009:adverse effects; D004195:Disease Models, Animal; D005260:Female; D016130:Immunophenotyping; D018655:Lymphocyte Count; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics*; D012720:Severity of Illness Index; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism*; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism*
chemical_list: D039481:CD11b Antigen; D039521:CD11c Antigen; D016207:Cytokines; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; D016264:Dextran Sulfate
keywords: Crohn's disease; T helper type 1/type 17; inflammatory bowel disease; miR-155−/−; ulcerative colitis