免疫(IMMUNITY)2013-09-05 2:57 AM

Immunity - miR-142-3p Prevents Macrophage Differentiation during Cancer-Induced Myelopoiesis

Tumor progression is accompanied by an altered myelopoiesis causing the accumulation of immunosuppressive cells. Here, we showed that miR-142-3p downregulation promoted macrophage differentiation and determined the acquisition of their immunosuppressive function in tumor. Tumor-released cytokines signaling through gp130, the common subunit of the interleukin-6 cytokine receptor family, induced the LAP∗ isoform of C/EBPβ transcription factor, promoting macrophage generation. miR-142-3p downregulated gp130 by canonical binding to its messenger RNA (mRNA) 3' UTR and repressed C/EBPβ LAP∗ by noncanonical binding to its 5' mRNA coding sequence. Enforced miR expression impaired macrophage differentiation both in vitro and in vivo. Mice constitutively expressing miR-142-3p in the bone marrow showed a marked increase in survival following immunotherapy with tumor-specific T lymphocytes. By modulating a specific miR in bone marrow precursors, we thus demonstrated the feasibility of altering tumor-induced macrophage differentiation as a potent tool to improve the efficacy of cancer immunotherapy.

KEYWORDS

SHARE & LIKE

COMMENTS

ABOUT THE AUTHOR

免疫(IMMUNITY)

0 Following 2 Fans 0 Projects 45 Articles

SIMILAR ARTICLES

T cell receptor (TCR) signaling driven by interaction of the TCR with specific complexes of self-peptide and the major histocompatibility complex deter

Read More

A20 is an anti-inflammatory protein linked to multiple human autoimmune diseases and lymphomas. A20 possesses a deubiquitinating motif and a zinc finge

Read More

Human linkage analyses have implicated the MS4A2-containing gene locus (encoding FcεRIβ) as a candidate for allergy susceptibility. We have identified

Read More

The transcription factor IRF4 regulates immunoglobulin class switch recombination and plasma cell differentiation. Its differing concentrations appear

Read More

The mechanisms underlying the silencing of alternative fate potentials in very early B cell precursors remain unclear. Using gain- and loss-of-function

Read More

Macrophage and dendritic cell (DC) progenitors (MDPs) and common DC progenitors (CDPs) are bone marrow (BM) progenitors with DC differentiation potenti

Read More

CD103+CD11b+ dendritic cells (DCs) represent the major migratory DC population within the small intestinal lamina propria (SI-LP), but their in vivo fu

Read More

Mouse and human dendritic cells (DCs) are composed of functionally specialized subsets, but precise interspecies correlation is currently incomplete. H

Read More

Regulation of metabolic pathways in the immune system provides a mechanism to actively control cellular function, growth, proliferation, and survival.

Read More

At sites of inflammation, certain regulatory T cells (Treg cells) can undergo rapid reprogramming into helper-like cells without loss of the transcript

Read More