title: Regulation of monocyte functional heterogeneity by miR-146a and Relb.
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.
authors.affiliation: Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Etzrodt
authors.forename: Virna
authors.initials: V
authors.lastname: Cortez-Retamozo
authors.forename: Andita
authors.initials: A
authors.lastname: Newton
authors.forename: Jimmy
authors.initials: J
authors.lastname: Zhao
authors.forename: Aylwin
authors.initials: A
authors.lastname: Ng
authors.forename: Moritz
authors.initials: M
authors.lastname: Wildgruber
authors.forename: Pedro
authors.initials: P
authors.lastname: Romero
authors.forename: Thomas
authors.initials: T
authors.lastname: Wurdinger
authors.forename: Ramnik
authors.initials: R
authors.lastname: Xavier
authors.forename: Frederic
authors.initials: F
authors.lastname: Geissmann
authors.forename: Etienne
authors.initials: E
authors.lastname: Meylan
authors.forename: Matthias
authors.initials: M
authors.lastname: Nahrendorf
authors.forename: Filip K
authors.initials: FK
authors.lastname: Swirski
authors.forename: David
authors.initials: D
authors.lastname: Baltimore
authors.forename: Ralph
authors.initials: R
authors.lastname: Weissleder
authors.forename: Mikael J
authors.initials: MJ
authors.lastname: Pittet
mesh_terms: D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000502:physiology*; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D051841:Transcription Factor RelB / Q000378:metabolism / Q000502:physiology*
chemical_list: C542542:MIRN146 microRNA, human; D035683:MicroRNAs; C534190:Mirn146 microRNA, mouse; C497593:RELB protein, human; C497594:Relb protein, mouse; D051841:Transcription Factor RelB