IRF5-mediated immune responses and its implications in immunological disorders

Kaur, Ashwinder; Lee, Learn‐Han; Chow, Sek C.; Fang, Chee‐Mun

doi:10.1080/08830185.2018.1469629

Cited by 28 publications

(27 citation statements)

References 140 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…13 It senses danger signals and induces inflammatory gene expression, giving rise to M1 macrophages. 10 The silencing or a deficiency of Irf5 hampers M1 macrophage polarization, 1 and in our study, we also confirmed that the myeloid-specific ablation of Irf5 reduces M1 macrophage polarization in the intestines of mice affected by NEC.…”

Section: Discussionsupporting

confidence: 83%

“…35,36 Upon the activation of TLRs by various stimuli, IRF5 participates in promoting downstream pro-inflammatory signaling. 10 Considering the important role of TLRs in NEC, 37,38 it is reasonable that IRF5 may also be induced in NEC. Indeed, our data show that IRF5 is upregulated in NEC and, more importantly, that it is mainly induced in infiltrated macrophages.…”

Section: Discussionmentioning

confidence: 99%

“…6,9 Interferon regulatory factor 5 (IRF5) which is mainly expressed in immune cells, is involved in TLRs-mediated signal transduction and immune cell differentiation. 10 It has been revealed that IRF5 is crucial in the development of various autoimmune diseases, such as rheumatoid arthritis 11 and systemic lupus erythematosus. 12 Recent studies have further suggested that IRF5 plays a key role in polarizing macrophages towards a pro-inflammatory M1 phenotype, 13,14 and that IRF5 induction in macrophages promotes the pathogenesis of various inflammatory diseases including sepsis, 13,15 insulin resistance during obesity, 16 myocardial infarction, 17 and atherosclerosis.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Irf5 deficiency in myeloid cells prevents necrotizing enterocolitis by inhibiting M1 macrophage polarization

Wei

Tang

et al. 2019

Mucosal Immunology

View full text Add to dashboard Cite

Necrotizing enterocolitis (NEC) is a severe inflammatory disease and is the most common cause of gastrointestinal mortality in newborns. However, the mechanisms remain unclear. Interferon regulatory factor 5 (IRF5) is a master regulator of macrophage function, which is essential for proinflammatory M1 macrophage polarization, and our previous data suggest the role of M1 macrophages promote NEC injury. Here, we investigated whether IRF5 is involved in the pathogenesis of NEC. We found that IRF5 was induced in infiltrated macrophages in neonates with NEC compared to the controls. We further confirmed IRF5 induction in macrophages in murine experimental NEC, and the infiltrated macrophages were predominantly polarized into M1 but not M2 phenotype in NEC. We generated the myeloid‐specific IRF5 defecient mice, and revealed that myeloid‐specific deficiency of IRF5 dramatically prevented experimental NEC, which was associated with reduced M1 macrophage polarization and systematic inflammation. Moreover, we found that ablation of IRF5 in myeloid cells markedly suppressed intestinal epithelial cells apoptosis and further prevented intestinal barrier dysfunction induced by experimental NEC. Overall, our study provides evidence that IRF5 in myeloid cells participates in the pathogenesis of NEC, while myeloid cell‐deletion of IRF5 prevents NEC via inhibiting M1 macrophage polarization. Support or Funding Information This study was supported by the National Natural Science Foundation of China (81501298, 81670390, and 81670259). This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

show abstract

Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Irf5 deficiency in myeloid cells prevents necrotizing enterocolitis by inhibiting M1 macrophage polarization

Wei

Tang

et al. 2019

Mucosal Immunology

View full text Add to dashboard Cite

show abstract

“…Indeed, it was previously revealed that the IRF5 gene silencing suppressed levels of IRF5 in cardiac macrophages, reprogrammed their phenotype and supported the inflammatory resolution [58]. There are also some known IRF5 inhibitors [59], like TRIM28 or KAP1 [60], flavonoids called Baicalin (which simultaneously promotes M2 phenotype by IRF4 upregulation) [61] and Quercetin [62] or polyphenol called Mangiferin [63].…”

Section: Discussionmentioning

confidence: 99%

Monocytes of newly diagnosed juvenile DM1 patients are prone to differentiate into regulatory IL-10+ M2 macrophages

et al. 2019

View full text Add to dashboard Cite

Alternatively activated macrophages (M2) exert anti-inflammatory effects and are crucial for keeping balance between protective and destructive cell-mediated immunity in healing phase of inflammation. Two members of the interferon regulatory factors family, IRF5 and IRF4, are known to promote M1 or M2 phenotype, respectively. Our study aimed to analyse the effectiveness of the M2 differentiation process in vitro (achieved by IL-4 stimulation) and its relationship to the stage of type 1 diabetes mellitus (DM1) in juvenile patients. To identify the basic changes in M2 phenotype, we examined the expression of the surface CD206, CD14, CD86 molecules, intracellular IRF4 and IRF5 transcription factors as well as IL-10 and TNFα intracellular production. Ten newly diagnosed (ND-DM1) and ten long-standing (LS-DM1) patients were enrolled into the study. The control group consisted of six children. We observed a significantly higher number of unpolarised CD206 + CD14 + cells in the M2 cultures of DM1 subjects when compared to healthy ones. Examined cells presented common features with M1 macrophages (high levels of the CD14/CD86/IRF5 markers); however, they were weak TNFα producers in ND-DM1 patients. For the first time, we have revealed dysregulated IRF4/IRF5 axis in the analysed subpopulation derived from diabetic patients. Additionally, monocytes of ND-DM1 children were still able to differentiate into regulatory IL-10 + M2 macrophages, while this process was highly limited in LS-DM1 patients. Summarising, we suggest that the M2 polarisation process is less effective in DM1 patients than in healthy subjects and it may vary depending on the stage of disease. It can be concluded that in vitro differentiated M2 macrophages may be used in the future as inflammatory inhibitors for adoptive therapy experiments in ND-DM1 subjects.

show abstract

“…Accumulating data from several studies has shown that IRF5 is a critical mediator in developing Th1 responses associated with the pathogenesis of various diseases, including autoimmune, metabolic, and infectious diseases [43] . Conversely, studies have also demonstrated that IRF5 plays a role in inducing Th2 responses [44,45] .…”

Section: Interferon Regulatory Factors (Irfs) Familymentioning

confidence: 99%

An overview of the human immune system and the role of interferon regulatory factors (IRFs)

Kaur¹,

Fang²

2020

Prog Micobes Mol Biol

Self Cite

View full text Add to dashboard Cite

The immune system consists of a dynamic network of cells, proteins, tissues, and organs that communicate to provide adequate defense responses against pathogenic agents. The immune system divide into the non-specific (innate) and the specific (adaptive) components, where the interactions between these two arms are intricately regulated. To deploy effective immune responses, immune systems comprise various cells and molecules that communicate with each other via signaling pathways coordinated by gene regulatory networks. The interferon regulatory factors (IRFs) are critical regulators of both the immune system’s development and activation of different cells. To better understand the essential components of the normal immune system, this review essentially aims to cover the current knowledge of individual components of the immune system and the important role of IRFs in regulating the immune system.

show abstract

IRF5-mediated immune responses and its implications in immunological disorders

Cited by 28 publications

References 140 publications

Irf5 deficiency in myeloid cells prevents necrotizing enterocolitis by inhibiting M1 macrophage polarization

Irf5 deficiency in myeloid cells prevents necrotizing enterocolitis by inhibiting M1 macrophage polarization

Monocytes of newly diagnosed juvenile DM1 patients are prone to differentiate into regulatory IL-10+ M2 macrophages

An overview of the human immune system and the role of interferon regulatory factors (IRFs)

Contact Info

Product

Resources

About