MicroRNA-142 Is Critical for the Homeostasis and Function of Type 1 Innate Lymphoid Cells

Immunity. 2019 Sep 17;51(3):479-490.e6. doi: 10.1016/j.immuni.2019.06.016. Epub 2019 Aug 8.


Natural killer (NK) cells are cytotoxic type 1 innate lymphoid cells (ILCs) that defend against viruses and mediate anti-tumor responses, yet mechanisms controlling their development and function remain incompletely understood. We hypothesized that the abundantly expressed microRNA-142 (miR-142) is a critical regulator of type 1 ILC biology. Interleukin-15 (IL-15) signaling induced miR-142 expression, whereas global and ILC-specific miR-142-deficient mice exhibited a cell-intrinsic loss of NK cells. Death of NK cells resulted from diminished IL-15 receptor signaling within miR-142-deficient mice, likely via reduced suppressor of cytokine signaling-1 (Socs1) regulation by miR-142-5p. ILCs persisting in Mir142-/- mice demonstrated increased expression of the miR-142-3p target αV integrin, which supported their survival. Global miR-142-deficient mice exhibited an expansion of ILC1-like cells concurrent with increased transforming growth factor-β (TGF-β) signaling. Further, miR-142-deficient mice had reduced NK-cell-dependent function and increased susceptibility to murine cytomegalovirus (MCMV) infection. Thus, miR-142 critically integrates environmental cues for proper type 1 ILC homeostasis and defense against viral infection.

Keywords: IL-15; ILC1-like cells; NK cells; cytokine receptors; innate lymphoid cells; integrin; microRNA-142; murine cytomegalovirus; tissue resident.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Female
  • HEK293 Cells
  • Homeostasis / immunology*
  • Humans
  • Immunity, Innate / immunology*
  • Killer Cells, Natural / immunology
  • Lymphocytes / immunology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • MicroRNAs / immunology*
  • Muromegalovirus / immunology
  • NIH 3T3 Cells
  • Receptors, Interleukin-15 / immunology
  • Signal Transduction / immunology
  • Suppressor of Cytokine Signaling Proteins / immunology
  • Transforming Growth Factor beta / immunology


  • MicroRNAs
  • Mirn142 microRNA, mouse
  • Receptors, Interleukin-15
  • Suppressor of Cytokine Signaling Proteins
  • Transforming Growth Factor beta