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Published August 2012 | public
Journal Article

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

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.

Additional Information

© 2012 Elsevier-Science Inc.

Additional details

Created:
August 19, 2023
Modified:
October 18, 2023