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J Exp Med. 2017 Dec 4;214(12):3627-3643. doi: 10.1084/jem.20170545. Epub 2017 Nov 9.

MicroRNA regulation of type 2 innate lymphoid cell homeostasis and function in allergic inflammation.

Author information

1
Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA.
2
Sandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA.
3
Department of Pathology, University of California, San Francisco, San Francisco, CA.
4
Department of Medicine, University of California, San Francisco, San Francisco, CA.
5
Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA.
6
Institute for Immunology, Biomedical Center Munich, Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany.
7
Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA mark.ansel@ucsf.edu.

Abstract

MicroRNAs (miRNAs) exert powerful effects on immunity through coordinate regulation of multiple target genes in a wide variety of cells. Type 2 innate lymphoid cells (ILC2s) are tissue sentinel mediators of allergic inflammation. We established the physiological requirements for miRNAs in ILC2 homeostasis and immune function and compared the global miRNA repertoire of resting and activated ILC2s and T helper type 2 (TH2) cells. After exposure to the natural allergen papain, mice selectively lacking the miR-17∼92 cluster in ILC2s displayed reduced lung inflammation. Moreover, miR-17∼92-deficient ILC2s exhibited defective growth and cytokine expression in response to IL-33 and thymic stromal lymphopoietin in vitro. The miR-17∼92 cluster member miR-19a promoted IL-13 and IL-5 production and inhibited expression of several targets, including SOCS1 and A20, signaling inhibitors that limit IL-13 and IL-5 production. These findings establish miRNAs as important regulators of ILC2 biology, reveal overlapping but nonidentical miRNA-regulated gene expression networks in ILC2s and TH2 cells, and reinforce the therapeutic potential of targeting miR-19 to alleviate pathogenic allergic responses.

PMID:
29122948
PMCID:
PMC5716040
DOI:
10.1084/jem.20170545
[Indexed for MEDLINE]
Free PMC Article

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