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

Melissa M. Berrien-Elliott, Yaping Sun, Carly Neal, Aaron Ireland, Maria C. Trissal, Ryan P. Sullivan, Julia A. Wagner, Jeffrey W. Leong, Pamela Wong, Annelise Y. Mah-Som, Terrence N. Wong, Timothy Schappe, Catherine R. Keppel, Victor S. Cortez, Efstathios G. Stamatiades, Ming O. Li, Marco Colonna, Daniel C. Link, Anthony R. French, Megan A. CooperWei Le Wang, Mark P. Boldin, Pavan Reddy, Todd A. Fehniger

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)479-490.e6
JournalImmunity
Volume51
Issue number3
DOIs
StatePublished - Sep 17 2019

Keywords

  • IL-15
  • ILC1-like cells
  • NK cells
  • cytokine receptors
  • innate lymphoid cells
  • integrin
  • microRNA-142
  • murine cytomegalovirus
  • tissue resident

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