MicroRNA Let-7f: A Novel Regulator of Innate Immune Response in Human Endocervical Cells

作者:Sathe Ameya; Patgaonkar Mandar S; Bashir Tahir; Reddy Kudumula Venkata Rami*
来源:American Journal of Reproductive Immunology, 2014, 71(2): 137-153.
DOI:10.1111/aji.12165

摘要

ProblemEndocervical epithelial cells express pattern recognition receptors (PRRs) that aid in innate immune responses. Mechanisms regulating signaling of PRRs are poorly understood.
Methods of StudyEndocervical cells (End1/E6E7) were treated with ligands of TLR9 and RIG-I once or after pre-stimulation with same ligand. Cytokine responses were determined by ELISA. Differential gene expression was analyzed by microarray. Differentially expressed genes were validated by qPCR /Western blot. Role of let-7f was studied by inhibition and over-expression studies using commercial inhibitors and let-7f encoding plasmids, respectively.
ResultsSingle stimulation of cells with TLR9 ligand, but not RIG-I ligand, induced tolerance to subsequent challenge to the same ligand. Stimulation with TLR9 decreased let-7f and increased its target Blimp-1. Conversely, RIG-I stimulation increased let-7f and decreased Blimp-1 expression. Inhibition and over-expression revealed let-7f is involved in induction of immune tolerance.
ConclusionWe identify let-7f as a novel regulator of PRR signaling in endocervical cells.

  • 出版日期2014-2