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MicroRNAs 24 and 27 Suppress Allergic Inflammation and Target a Network of
Regulators of T Helper 2 Cell-Associated Cytokine Production
#MMPMID26850657
Pua HH
; Steiner DF
; Patel S
; Gonzalez JR
; Ortiz-Carpena JF
; Kageyama R
; Chiou NT
; Gallman A
; de Kouchkovsky D
; Jeker LT
; McManus MT
; Erle DJ
; Ansel KM
Immunity
2016[Apr]; 44
(4
): 821-32
PMID26850657
show ga
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.