We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Excessive expression of miR-27 impairs Treg-mediated immunological tolerance.
- Authors
Cruz, Leilani O.; Hashemifar, Somaye Sadat; Cheng-Jang Wu; Sunglim Cho; Nguyen, Duc T.; Ling-Li Lin; Aly Azeem Khan; Li-Fan Lu; Wu, Cheng-Jang; Cho, Sunglim; Lin, Ling-Li; Khan, Aly Azeem; Lu, Li-Fan
- 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.
- Subjects
GENE expression; MICRORNA genetics; IMMUNOLOGICAL tolerance; IMMUNE system; PHENOTYPES; T cells; CELL differentiation; GENETICS
- Publication
Journal of Clinical Investigation, 2017, Vol 127, Issue 2, p530
- ISSN
0021-9738
- Publication type
journal article
- DOI
10.1172/JCI88415