Regulation of Monocyte Functional Heterogeneity by MiR-146a and Relb

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2012 May 1

PMID 22545247

Citations 68

Authors

Martin Etzrodt

Virna Cortez-Retamozo

Andita Newton

Jimmy Zhao

Aylwin Ng

Moritz Wildgruber

Pedro Romero

Thomas Wurdinger

Ramnik Xavier

Frederic Geissmann

Etienne Meylan

Matthias Nahrendorf

Filip K Swirski

David Baltimore

Ralph Weissleder

Mikael J Pittet

Affiliations

Soon will be listed here.

Abstract

Monocytes serve as a central defense system against infection and injury but can also promote pathological inflammatory responses. Considering the evidence that monocytes exist in at least two subsets committed to divergent functions, we investigated whether distinct factors regulate the balance between monocyte subset responses in vivo. We identified a microRNA (miRNA), miR-146a, which is differentially regulated both in mouse (Ly-6C(hi)/Ly-6C(lo)) and human (CD14(hi)/CD14(lo)CD16(+)) monocyte subsets. The single miRNA controlled the amplitude of the Ly-6C(hi) monocyte response during inflammatory challenge whereas it did not affect Ly-6C(lo) cells. miR-146a-mediated regulation was cell-intrinsic and depended on Relb, a member of the noncanonical NF-κB/Rel family, which we identified as a direct miR-146a target. These observations not only provide mechanistic insights into the molecular events that regulate responses mediated by committed monocyte precursor populations but also identify targets for manipulating Ly-6C(hi) monocyte responses while sparing Ly-6Clo monocyte activity.

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