title: Excessive expression of miR-27 impairs Treg-mediated immunological tolerance.
abstract: MicroRNAs (miRs) are tightly regulated in the immune system, and aberrant expression of miRs often results in hematopoietic malignancies and autoimmune diseases. Previously, it was suggested that elevated levels of miR-27 in T cells isolated from patients with multiple sclerosis facilitate disease progression by inhibiting Th2 immunity and promoting pathogenic Th1 responses. Here we have demonstrated that, although mice with T cell-specific overexpression of miR-27 harbor dysregulated Th1 responses and develop autoimmune pathology, these disease phenotypes are not driven by miR-27 in effector T cells in a cell-autonomous manner. Rather, dysregulation of Th1 responses and autoimmunity resulted from a perturbed Treg compartment. Excessive miR-27 expression in murine T cells severely impaired Treg differentiation. Moreover, Tregs with exaggerated miR-27-mediated gene regulation exhibited diminished homeostasis and suppressor function in vivo. Mechanistically, we determined that miR-27 represses several known as well as previously uncharacterized targets that play critical roles in controlling multiple aspects of Treg biology. Collectively, our data show that miR-27 functions as a key regulator in Treg development and function and suggest that proper regulation of miR-27 is pivotal to safeguarding Treg-mediated immunological tolerance.
authors.forename: Leilani O
authors.initials: LO
authors.lastname: Cruz
authors.forename: Somaye Sadat
authors.initials: SS
authors.lastname: Hashemifar
authors.forename: Cheng-Jang
authors.initials: CJ
authors.lastname: Wu
authors.forename: Sunglim
authors.initials: S
authors.lastname: Cho
authors.forename: Duc T
authors.initials: DT
authors.lastname: Nguyen
authors.forename: Ling-Li
authors.initials: LL
authors.lastname: Lin
authors.forename: Aly Azeem
authors.initials: AA
authors.lastname: Khan
authors.forename: Li-Fan
authors.initials: LF
authors.lastname: Lu
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology*; D007108:Immune Tolerance; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D035683:MicroRNAs; C540674:Mirn27 microRNA, mouse