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

2019; Cell Press; Volume: 51; Issue: 3 Linguagem: Inglês

10.1016/j.immuni.2019.06.016

1097-4180

Melissa M. Berrien-Elliott, Yaping Sun, Carly C. Neal, Aaron R. Ireland, Maria Trissal, Ryan P. Sullivan, Julia A. Wagner, Jeffrey 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. Cooper, Wei-Le Wang, Mark Boldin, Pavan Reddy, Todd A. Fehniger,

Reproductive System and Pregnancy

Summary 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.