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

Authors

  • Ameya Sathe,

    1. Division of Molecular Immunology and Microbiology (MIM), National Institute for Research in Reproductive Health (ICMR), Mumbai, India
    Search for more papers by this author
  • Mandar S. Patgaonkar,

    1. Department of Biological Sciences, Tata Institute for Fundamental Research, Mumbai, India
    Search for more papers by this author
  • Tahir Bashir,

    1. Division of Molecular Immunology and Microbiology (MIM), National Institute for Research in Reproductive Health (ICMR), Mumbai, India
    Search for more papers by this author
  • Kudumula Venkata Rami Reddy

    Corresponding author
    1. Division of Molecular Immunology and Microbiology (MIM), National Institute for Research in Reproductive Health (ICMR), Mumbai, India
    • Correspondence

      K. V. R. Reddy, Division of Molecular Immunology and Microbiology (MIM), National Institute for Research in Reproductive Health (ICMR), J.M. Street, Parel, Mumbai 400012, India. E-mail: reddyk@nirrh.res.in

    Search for more papers by this author

Abstract

Problem

Endocervical epithelial cells express pattern recognition receptors (PRRs) that aid in innate immune responses. Mechanisms regulating signaling of PRRs are poorly understood.

Methods of Study

Endocervical 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.

Results

Single 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.

Conclusion

We identify let-7f as a novel regulator of PRR signaling in endocervical cells.

Ancillary