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

被引：108

作者：

Etzrodt, Martin ^{[1
]}

Cortez-Retamozo, Virna ^{[1
]}

Newton, Andita ^{[1
]}

Zhao, Jimmy ^{[4
]}

Ng, Aylwin ^{[2
,3
]}

Wildgruber, Moritz ^{[1
]}

Romero, Pedro ^{[5
]}

Wurdinger, Thomas ^{[6
]}

Xavier, Ramnik ^{[2
,3
]}

Geissmann, Frederic ^{[7
]}

Meylan, Etienne ^{[8
]}

Nahrendorf, Matthias ^{[1
]}

Swirski, Filip K. ^{[1
]}

Baltimore, David ^{[4
]}

Weissleder, Ralph ^{[1
,9
]}

Pittet, Mikael J. ^{[1
]}

机构：

[1] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA

[2] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA 02114 USA

[3] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA

[4] CALTECH, Div Biol, Pasadena, CA 91125 USA

[5] Ludwig Ctr Canc Res, CH-1005 Lausanne, Switzerland

[6] Vrije Univ Amsterdam, Med Ctr, Canc Ctr Amsterdam, NL-1080 Amsterdam, Netherlands

[7] Kings Coll London, Ctr Mol & Cellular Biol Inflammat, London SE1 1UL, England

[8] Ecole Polytech Fed Lausanne, Swiss Inst Expt Canc Res, CH-1015 Lausanne, Switzerland

[9] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA

来源：

CELL REPORTS | 2012年 / 1卷 / 04期

基金：

美国国家卫生研究院;

关键词：

DENDRITIC CELLS; IMMUNE-SYSTEM; MACROPHAGES; SUBSETS; DIFFERENTIATION; INFLAMMATION; EXPRESSION; MICRORNAS; INFECTION; RISE;

D O I：

10.1016/j.celrep.2012.02.009

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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-kappa B/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-6C(lo) monocyte activity.

引用

页码：317 / 324

页数：8

共 28 条

[11] Deficient CD40-TRAF6 signaling in leukocytes prevents atherosclerosis by skewing the immune response toward an antiinflammatory profile [J].