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

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

Author information

1
Department of Medicine, Division of Oncology, Washington University School of Medicine, Saint Louis, MO, USA.
2
Division of Hematology and Oncology, University of Michigan, Ann Arbor, MI, USA.
3
Department of Pediatrics, Division of Rheumatology, Washington University School of Medicine, Saint Louis, MO, USA.
4
Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO, USA.
5
Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
6
Department of Molecular and Cellular Biology, Beckman Research Institute of the City of Hope, Duarte, CA, USA.
7
Department of Medicine, Division of Oncology, Washington University School of Medicine, Saint Louis, MO, USA. Electronic address: tfehnige@wustl.edu.

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.

KEYWORDS:

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

PMID:
31402259
PMCID:
PMC6750984
[Available on 2020-09-17]
DOI:
10.1016/j.immuni.2019.06.016

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