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

Berrien-Elliott, Melissa M. and Sun, Yaping and Neal, Carly and Ireland, Aaron and Trissal, Maria C. and Sullivan, Ryan and Wagner, Julia A. and Leong, Jeffrey W. and Wong, Pamela and Mah-Som, Annelise Y. and Wong, Terrence N. and Schappe, Timothy and Keppel, Catherine R. and Cortez, Victor S. and Stamatiades, Efstathios G. and Li, Ming O. and Colonna, Marco and Link, Daniel C. and French, Anthony R. and Cooper, Megan A. and Wang, Wei-Le and Boldin, Mark P. and Reddy, Pavan and Fehniger, Todd A. (2019) MicroRNA-142 Is Critical for the Homeostasis and Function of Type 1 Innate Lymphoid Cells. Immunity. ISSN 10747613

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.

Item Type: Article
Date Deposited: 24 Aug 2019 00:45
Last Modified: 24 Aug 2019 00:45
URI: https://oak.novartis.com/id/eprint/40728

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