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Regulation of the LY-6CHI Monocyte Response by MIR-146A

Etzrodt, Martin and Cortez-Retamozo, Virna and Baltimore, David and Weissleder, Ralph and Pittet, Mikael (2012) Regulation of the LY-6CHI Monocyte Response by MIR-146A. Experimental Hematology, 40 (8). S75. ISSN 0301-472X. https://resolver.caltech.edu/CaltechAUTHORS:20120831-084546249

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Abstract

Monocytes exist in at least two distinct phenotypically and functionally committed subsets (‘inflammatory' Ly-6Chi and ‘resident' Ly-6Clo in mice). During the innate immune response the balance between monocyte subsets needs to be tightly regulated; however, which cell endogenous factors are involved in this process remain largely unknown. Here we identified miR-146a as a selective regulator of the inflammatory Ly-6Chi monocyte response. miR-146a is differentially expressed in Ly-6Chi and Ly-6Clo monocyte subsets in steady-state and can be selectively induced in Ly-6Chi cells upon inflammatory challenge. In competitive bone marrow chimera experiments miR-146a-/- Ly-6Chi monocytes outcompeted their wild-type counterparts accumulating at the site of inflammation. We found that miR-146a-/- mice displayed both elevated proliferation of monocytic precursors as well as increased recruitment of mature monocytes through higher expression of the chemokine receptor CCR2. Competitive co-adoptive transfer studies of granulocyte and macrophage progenitors (GMP) derived from wild-type and miR-146a-/- mice demonstrated that the phenotype selectively affected Ly-6Chi monocytes, but neither Ly-6Clo cells nor the granulocyte progeny and thus was cell intrinsic. We also identified Relb, a member of the non-canonical NF-κB/Rel family as a direct miR-146a target in Ly-6Chi monocytes. In conclusion miR-146a selectively regulates the amplitude of Ly-6Chi monocytes while it spares Ly-6Clo monocyte responses.


Item Type:Article
ORCID:
AuthorORCID
Baltimore, David0000-0001-8723-8190
Additional Information:© 2012 Elsevier-Science Inc.
Issue or Number:8
Record Number:CaltechAUTHORS:20120831-084546249
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20120831-084546249
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:33751
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:31 Aug 2012 16:38
Last Modified:03 Oct 2019 04:12

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