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Immunity. 2016 Apr 19;44(4):821-32. doi: 10.1016/j.immuni.2016.01.003. Epub 2016 Feb 2.

MicroRNAs 24 and 27 Suppress Allergic Inflammation and Target a Network of Regulators of T Helper 2 Cell-Associated Cytokine Production.

Author information

1
Department of Pathology, University of California, San Francisco, San Francisco, CA, USA.
2
Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA.
3
Diabetes Center, University of California, San Francisco, San Francisco, CA, USA.
4
Department of Pathology, University of California, San Francisco, San Francisco, CA, USA; Diabetes Center, University of California, San Francisco, San Francisco, CA, USA.
5
Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA; Diabetes Center, University of California, San Francisco, San Francisco, CA, USA.
6
Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
7
Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA; Sandler Asthma Basic Research Center, University of California, San Francisco, San Francisco CA, USA. Electronic address: mark.ansel@ucsf.edu.

Abstract

MicroRNAs (miRNAs) are important regulators of cell fate decisions in immune responses. They act by coordinate repression of multiple target genes, a property that we exploited to uncover regulatory networks that govern T helper-2 (Th2) cells. A functional screen of individual miRNAs in primary T cells uncovered multiple miRNAs that inhibited Th2 cell differentiation. Among these were miR-24 and miR-27, miRNAs coexpressed from two genomic clusters, which each functioned independently to limit interleukin-4 (IL-4) production. Mice lacking both clusters in T cells displayed increased Th2 cell responses and tissue pathology in a mouse model of asthma. Gene expression and pathway analyses placed miR-27 upstream of genes known to regulate Th2 cells. They also identified targets not previously associated with Th2 cell biology which regulated IL-4 production in unbiased functional testing. Thus, elucidating the biological function and target repertoire of miR-24 and miR-27 reveals regulators of Th2 cell biology.

PMID:
26850657
PMCID:
PMC4838571
DOI:
10.1016/j.immuni.2016.01.003
[Indexed for MEDLINE]
Free PMC Article

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