@article{df0b9c48fec54521b26d235ab0c321cb,
title = "MicroRNA-142 Is Critical for the Homeostasis and Function of Type 1 Innate Lymphoid Cells",
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",
author = "Berrien-Elliott, {Melissa M.} and Yaping Sun and Carly Neal and Aaron Ireland and Trissal, {Maria C.} and Sullivan, {Ryan P.} and Wagner, {Julia A.} and Leong, {Jeffrey W.} and Pamela Wong and Mah-Som, {Annelise Y.} and Wong, {Terrence N.} and Timothy Schappe and Keppel, {Catherine R.} and Cortez, {Victor S.} and Stamatiades, {Efstathios G.} and Li, {Ming O.} and Marco Colonna and Link, {Daniel C.} and French, {Anthony R.} and Cooper, {Megan A.} and Wang, {Wei Le} and Boldin, {Mark P.} and Pavan Reddy and Fehniger, {Todd A.}",
note = "Funding Information: We thank Dr. Mark Sands for providing reagents, Dr. Marina Cella for providing human RNA samples, and Dr. Timothy O{\textquoteright}Sullivan for useful discussions. This work was supported by NIH/NCI F32 CA200253 to M.M.B.-E.; NIH T32HL007088 to M.M.B-E., J.A.W., and R.P.S.; NIH R01AI078994 to A.R.F.; NIH U01AI095542 , R01DE025884 , and R01DK103039 to M.C.; NIH 5T32CA009547-30 to V.S.C.; Crohn's & Colitis Foundation of America 274415 , to M.C.; Howard Hughes Medical Institute Medical Fellow Award to J.A.W.; Rheumatology Research Foundation , NIH R01 AI127752 to M.A.C.; F30AI129110 , T32GM07200 to A.Y.M.; The American Association of Immunologists Fellowship A.Y.M. and M.A.C.; NIH CA-0173878 , NIH/NCI CA-143379 , and NHLBI/HL-090775 to P.R.; ASH Scholar Award from the American Society of Hematology Foundation , a Physician-Scientist Early Career Award from the Howard Hughes Medical Institute, and NIH R01AI102924 and R01CA205239 to T.A.F. Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",
year = "2019",
month = sep,
day = "17",
doi = "10.1016/j.immuni.2019.06.016",
language = "English",
volume = "51",
pages = "479--490.e6",
journal = "Immunity",
issn = "1074-7613",
number = "3",
}