IRF5 promotes inflammatory macrophage polarization and TH1-TH17 responses

  title={IRF5 promotes inflammatory macrophage polarization and TH1-TH17 responses},
  author={Thomas Krausgruber and Katrina Blazek and Tim Smallie and Saba Alzabin and Helen E. Lockstone and Natasha Sahgal and Tracy Hussell and Marc Feldmann and Irina A. Udalova},
  journal={Nature Immunology},
Polymorphisms in the gene encoding the transcription factor IRF5 that lead to higher mRNA expression are associated with many autoimmune diseases. Here we show that IRF5 expression in macrophages was reversibly induced by inflammatory stimuli and contributed to the plasticity of macrophage polarization. High expression of IRF5 was characteristic of M1 macrophages, in which it directly activated transcription of the genes encoding interleukin 12 subunit p40 (IL-12p40), IL-12p35 and IL-23p19 and… 

MEF2C promotes M1 macrophage polarization and Th1 responses.

It is shown that myocyte enhancer factor 2 C (MEF2C) is essential for regulating M1 macrophage polarization in response to infection and inflammation and is identified as a potential target for therapeutic intervention in inflammatory and autoimmune diseases.

IRF5 Is a Specific Marker of Inflammatory Macrophages In Vivo

It is shown that murine bone marrow derived macrophages differentiated in vitro with GM-CSF are also characterised by high levels of IRF5 mRNA and protein and express proinflammatory cytokines upon LPS stimulation.

Epigenetic and transcriptional regulation of IL4-induced CCL17 production in human monocytes and murine macrophages

Evidence is presented that IL4 up-regulates IRF4 expression at the epigenetic level by enhancing the expression and activity of jumonji domain–containing protein 3 (JMJD3) demethylase, which appears to share elements of a common signaling pathway in regulating CCL17 production in human monocytes and murine macrophages.

NFAT5-Regulated Macrophage Polarization Supports the Proinflammatory Function of Macrophages and T Lymphocytes

Detailed analysis of the effect of NFAT5 in pro- and anti-inflammatory macrophages uncovered its ability to regulate distinct genes under both polarization modes and revealed its predominant role in promoting pro inflammatory macrophage functions.

IRF5:RelA Interaction Targets Inflammatory Genes in Macrophages

Macrophages: A transcription factor to call their own

The data indicate that the expression of GM-CSF at sites of inflammation can drive M1 macrophage polarization through increased IRF5 expression, which has both positive and negative effects on the transcription ofmacrophage subset-specific genes, known to drive pro-inflammatory T helper 1 (TH1) cell responses.

Notch-RBP-J Signaling Regulates IRF8 to Promote Inflammatory Macrophage Polarization

A signaling network in which signaling via Notch–RBP-J and TLRs is integrated at the level of synthesis of IRF8 protein is defined and a mechanism by which heterologous signaling pathways can regulate the TLR-induced inflammatory polarization of macrophages is identified.

IFN-γ Priming of Macrophages Represses a Part of the Inflammatory Program and Attenuates Neutrophil Recruitment

Macrophages form a heterogeneous population of immune cells, which is critical for both the initiation and resolution of inflammation. They can be skewed to a proinflammatory subtype by the Th1



IRF5 is required for late-phase TNF secretion by human dendritic cells.

This study provides new insights into diverse molecular mechanisms employed by IRF5 to regulate gene expression and implicates RelA-IRF5 interactions as a putative target for cell-specific modulation of TNF expression.

Integral role of IRF-5 in the gene induction programme activated by Toll-like receptors

The transcription factor IRF-5 is identified as a new, principal downstream regulator of the TLR–MyD88 signalling pathway and a potential target of therapeutic intervention to control harmful immune responses.

Tolerance and M2 (alternative) macrophage polarization are related processes orchestrated by p50 nuclear factor κB

Cells of the monocyte–macrophage lineage play a central role in the orchestration and resolution of inflammation. Plasticity is a hallmark of mononuclear phagocytes, and in response to environmental

Macrophage activation and polarization.

The main functions of polarized macrophages are reviewed and the perspectives of this field are discussed, which include high endocytic clearance capacities and trophic factor synthesis, accompanied by reduced pro-inflammatory cytokine secretion.

Negative regulation of Toll-like-receptor signaling by IRF-4.

It is shown that IRF-4 also interacts with MyD88 and acts as a negative regulator of TLR signaling, which may provide an insight into the complex regulatory mechanisms of MyD 88 signaling by IRFs.

Dual specificity phosphatase 1 (DUSP1) regulates a subset of LPS-induced genes and protects mice from lethal endotoxin shock

A specific regulatory role of DUSP1 is identified in controlling a subset of LPS-induced genes that determines the outcome of endotoxin shock, including IL-6 and IL-10 as well as the chemokines CCL3, CCL4, and CXCL2.

A Proximal κB Site in the IL-23 p19 Promoter Is Responsible for RelA- and c-Rel-Dependent Transcription

Investigation of mRNA levels in NF-κB-deficient macrophages provides the evidence that the association of RelA and c-Rel with the proximal κB site in the p19 promoter is required to induce of p19 expression.

Differential Regulation of Interleukin (IL)-12 p35 and p40 Gene Expression and Interferon (IFN)-γ–primed IL-12 Production by IFN Regulatory Factor 1

It is demonstrated that the levels of IL-12 p35 protein stimulated by IFN-γ and lipopolysaccharide (LPS) correspond to those of its mRNA, and that the nuclear factor κB signaling pathway is essential for the induction of IL's p35 transcription by LPS.

IL-17 and Th17 Cells.

The investigation of the differentiation, effector function, and regulation of Th17 cells has opened up a new framework for understanding T cell differentiation and now appreciate the importance of Th 17 cells in clearing pathogens during host defense reactions and in inducing tissue inflammation in autoimmune disease.