IRF5 Is a Specific Marker of Inflammatory Macrophages<i>In Vivo</i>

Weiss, Miriam; Blazek, Katrina; Byrne, Adam; Perocheau, Dany; Udalova, Irina A.

doi:10.1155/2013/245804

Cited by 109 publications

(99 citation statements)

References 41 publications

(50 reference statements)

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“…Here, we used human GM‐CSF and M‐CSF to polarize rabbit macrophages from peripheral blood monocytes, because there are no commercially available rabbit recombinant proteins for polarization of rabbit macrophages. When applied to murine macrophages, recombinant human M‐CSF induces the M2 phenotype, but human GM‐CSF does not induce the M1 phenotype in mice 21. Human M‐CSF and GM‐CSF share 83% and 69% amino acid identity with corresponding regions of rabbit M‐CSF and GM‐CSF, and 81% and 55% with mouse, respectively (data from National Center for Biotechnology Information; http://www.ncbi.nlm.nih.gov/).…”

Section: Discussionmentioning

confidence: 99%

Rabbit M1 and M2 macrophages can be induced by human recombinant GM‐CSF and M‐CSF

Yamane

Leung

2016

FEBS Open Bio

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Macrophages can change their phenotype in response to environmental cues. Polarized macrophages are broadly classified into two groups: classical activated M1 and alternative activated M2. Characterization of human macrophages has been widely studied, but polarized macrophages in rabbits have not been characterized. We characterized rabbit macrophages that were polarized using human recombinant GM‐CSF and M‐CSF. GM‐CSF‐treated macrophages had higher mRNA expression of proinflammatory cytokines (M1 phenotype) than did the M‐CSF‐treated counterpart. By contrast, high levels of TGF‐β and IL‐10 expression (M2 phenotype) were found in M‐CSF‐treated macrophages. The present study may be useful to understand roles of polarized macrophages in rabbit disease models.

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Section: Discussionmentioning

confidence: 99%

Rabbit M1 and M2 macrophages can be induced by human recombinant GM‐CSF and M‐CSF

Yamane

Leung

2016

FEBS Open Bio

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“…This was accomplished by immunohistochemistry, where double stainings were performed for Mac3 (general macrophage marker) in combination with IRF5, YM1, or IL-10 to identify M1-dominant, M2-dominant, and anti-inflammatory macrophages, respectively. IRF5 has been shown to be a specific marker for M1-dominant macrophages in vivo and in vitro (9,27), inducing transcription of genes encoding IL-12 and IL-23 and suppressing the gene encoding IL-10 in diverse disease settings. YM1 is a unique marker for M2-dominant macrophages in the lung (4,23).…”

Section: Discussionmentioning

confidence: 99%

Distinct macrophage phenotypes in allergic and nonallergic lung inflammation

Robbe

Draijer

Borg

et al. 2015

American Journal of Physiology-Lung Cellular and Molecular Phys

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Chronic exposure to farm environments is a risk factor for nonallergic lung disease. In contrast to allergic asthma, in which type 2 helper T cell (Th2) activation is dominant, exposure to farm dust extracts (FDE) induces Th1/Th17 lung inflammation, associated with neutrophil infiltration. Macrophage influx is a common feature of both types of lung inflammation, allergic and nonallergic. However, macrophage functions and phenotypes may vary according to their polarized state, which is dependent on the cytokine environment. In this study, we aimed to characterize and quantify the lung macrophage populations in two established murine models of allergic and nonallergic lung inflammation by means of fluorescence-activated cell sorting and immunohistochemistry. We demonstrated that, whereas in allergic asthma M2-dominant macrophages predominated in the lungs, in nonallergic inflammation M1-dominant macrophages were more prevalent. This was confirmed in vitro using a macrophage cell line, where FDE exerted a direct effect on macrophages, inducing M1-dominant polarization. The polarization of macrophages diverged depending on the exposure and inflammatory status of the tissue. Interfering with this polarization could be a target for treatment of different types of lung inflammation.

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“…The model is characterized by infiltration of polymorphonuclear and mononuclear cells, pannus formation, and erosion of bone and cartilage (17), and is Th17 dependent (18). We have previously reported that synovial macrophages from the AIA-affected joints are characterized by high levels of IRF5 (16). Here, we aimed to determine the role that IRF5 plays in synovial physiology and function in both naïve joints and during inflammatory arthritis.…”

Section: Significancementioning

confidence: 98%

“…We have documented the importance of the transcription factor IFN regulatory factor 5 (IRF5) in defining the classical inflammatory phenotype of macrophages (15,16). IRF5 has also recently been reported to be expressed in neutrophils, specifically in neutrophils from synovial fluid of arthritic mice (13).…”

mentioning

confidence: 99%

IRF5 controls both acute and chronic inflammation

Weiss

Byrne

Blazek

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Whereas the importance of macrophages in chronic inflammatory diseases is well recognized, there is an increasing awareness that neutrophils may also play an important role. In addition to the well-documented heterogeneity of macrophage phenotypes and functions, neutrophils also show remarkable phenotypic diversity among tissues. Understanding the molecular pathways that control this heterogeneity should provide abundant scope for the generation of more specific and effective therapeutics. We have shown that the transcription factor IFN regulatory factor 5 (IRF5) polarizes macrophages toward an inflammatory phenotype. IRF5 is also expressed in other myeloid cells, including neutrophils, where it was linked to neutrophil function. In this study we explored the role of IRF5 in models of acute inflammation, including antigen-induced inflammatory arthritis and lung injury, both involving an extensive influx of neutrophils. Mice lacking IRF5 accumulate far fewer neutrophils at the site of inflammation due to the reduced levels of chemokines important for neutrophil recruitment, such as the chemokine (C-X-C motif) ligand 1. Furthermore we found that neutrophils express little IRF5 in the joints and that their migratory properties are not affected by the IRF5 deficiency. These studies extend prior ones suggesting that inhibiting IRF5 might be useful for chronic macrophage-induced inflammation and suggest that IRF5 blockade would ameliorate more acute forms of inflammation, including lung injury.macrophages | neutrophils | IRF5 | acute inflammation | arthritis

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IRF5 Is a Specific Marker of Inflammatory MacrophagesIn Vivo

Cited by 109 publications

References 41 publications

Rabbit M1 and M2 macrophages can be induced by human recombinant GM‐CSF and M‐CSF

Rabbit M1 and M2 macrophages can be induced by human recombinant GM‐CSF and M‐CSF

Distinct macrophage phenotypes in allergic and nonallergic lung inflammation

IRF5 controls both acute and chronic inflammation

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