Expression and clinical significance of interferon regulatory factor 4 and soluble suppression of tumorigenesis 2 in conjunctival epithelial cells and tears of patients with dry eye / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the expression and clinical significance of interferon regulatory factor 4(IRF4)and soluble suppression of tumorigenesis 2(sST2)in conjunctival epithelial cells and tears of patients with dry eye.METHODS: A total of 94 patients with dry eye who admitted to our hospital from January 2019 to December 2021 were selected as the dry eye group, and 97 physical examiners who underwent ophthalmic examination were selected as the control group at the same time. The conjunctival epithelial cells and tears of the subjects were collected, and the clinical indicators, including tear film break-up time(BUT), corneal fluorescein staining(CFS)score, and Schirmer Ⅰ test(SⅠt)were recorded. The levels of IRF4 and sST2 in conjunctival epithelial cells were detected by quantitative real-time polymerase chain reaction(qRT-PCR), and the levels of IRF4 and sST2 in tears were detected by enzyme-linked immunosorbent assay(ELISA). Pearson method was used to analyze the correlation between IRF4 and sST2 levels in conjunctival epithelial cells and tears and clinical indicators of dry eye patients.RESULTS: The levels of IRF4 and sST2 in conjunctival epithelial cells and tears in dry eye group before treatment were significantly higher than those in control group(P<0.001). The levels of IRF4 and sST2 in conjunctival epithelial cells and tears of dry eye patients at 4wk after treatment were significantly lower than those before treatment(P<0.001). The BUT and SⅠt of dry eye patients increased significantly at 4wk after treatment, and the CFS score decreased significantly(P<0.001). The levels of IRF4 and sST2 in conjunctival epithelial cells and tears of dry eye patients before treatment were positively correlated with CFS score before treatment and negatively correlated with BUT and SⅠt before treatment(P<0.001).CONCLUSION: The levels of IRF4 and sST2 in conjunctival epithelial cells and tears of patients with dry eye are increased, and are significantly correlated with BUT, SⅠt and CFS scores, which has potential to become a new therapeutic target for dry eye.

Pirfenidone inhibits the polarization of M2 macrophages by down-regulating IRF4 to reduce the occurrence and development of radiation-induced lung fibrosis / 中华放射肿瘤学杂志

Objective:To explore the preventive and therapeutic effect of pirfenidone (PFD) on radiation-induced lung fibrosis (RILF) and its mechanism.Methods:40 female C57/BL6 mice were randomly divided into 4 groups: negative control group (NC), PFD treatment group (PFD), radiation treatment group (RT) and radiation plus PFD treatment group (RT+ PFD). Mice in RT and RT+ PFD groups received a single whole lung X-ray consisting of a 50 Gy dose of radiation, delivered by small animal radiation research platform (SARRP). PFD at a dose of 300 mg/kg was administered orally 2 h before irradiation for 150 d. HE and Masson staining were used to detect the infiltration of inflammatory cells and the degree of pulmonary fibrosis. Quantitative real-time PCR (qPCR) and Western blotting (WB) were adopted to detect the expression levels of M1/M2 macrophage phenotypic markers. The expression levels of arginase-1(ARG-1), chitinase 3-like protein 3(YM-1) and interferon regulatory factor-4(IRF4) of macrophages stimulated with IL-4 and IL-13 were detected by WB. In addition, immunofluorescence staining was used to detect the expression and translocation of IRF4 in macrophages among different treatment groups.Results:HE and Masson staining showed that PFD could significantly inhibit radiation-induced infiltration of inflammatory cells and fibrosis in lung tissues. The M2 macrophages and expression levels of ARG-1 and YM-1 were down-regulated in the RT+ PFD group. Cell experiments further confirmed that PFD could significantly inhibit the polarization of macrophages to M2 induced by IL-4+ IL-13, which was mainly related to the down-regulation of IRF4.Conclusion:PFD has a preventive and therapeutic effect on RILF by inhibiting IRF4 and reducing the polarization of macrophages to M2.

Progress of interferon regulatory factor 4-related lymphoma / 白血病·淋巴瘤

Interferon regulatory factor 4 (IRF4) is a member of IRF family, which is mainly expressed in lymphocytes and plays an important role in the development of lymphoma. In addition, it is related with a tentative classification in the name of large B-cell lymphoma with IRF4 gene rearrangement proposed in 2016 updated version of World Health Organization (WHO). This article reviews the structural features, biological functions of IRF4 gene, its role in lymphocyte development, and large B-cell lymphoma with IRF4 gene rearrangement.

An unusual presentation of large B-cell lymphoma with interferon regulatory factor 4 gene rearrangement

Rearrangements involving interferon regulatory factor 4 (IRF4) gene has been recently described in a subtype of diffuse large B-cell lymphoma (DLBCL). They occur in a typical clinical setting of a pediatric age group, predominantly with tonsillar mass, usually as a low-stage disease and with good response to chemotherapy. Histomorphologically, they show nodular/follicular architecture with diffuse strong immunopositivity for multiple myeloma oncogene 1. Here, the authors describe one such unusual case of large B-cell lymphoma with IRF4 gene rearrangement in a young child with the unusual location of inguinal region and detailed pathological (histological, immunohistochemical, and molecular) findings.

Association between AOX1, IRF4 methylation in peripheral blood leukocyte DNA and the risks of breast cancer: a case-control study / 中华流行病学杂志

Objective To understand the relationship between AOX1,IRF4 gene methylation status in peripheral blood leukocyte DNA,as well as its interaction with environmental factors,and the risk of breast cancer.Methods A case-control study was conducted among 401 breast cancer patients and 555 cancer-free controls selected from 2010 to 2014.Methylation sensitive-high resolution melting curve analysis was used to detect the methylation status of AOX1 and IRF4.The multiplication interaction effect between genes' methylation and environmental factors on the risk of breast cancer was analyzed by using unconditional logistic regression,and Excel software was used to analyze the additive interaction effect.Results Individuals without AOX1 methylation had a 1.37-fold (95％ CI:1.02-1.84) higher breast cancer risk compared to individuals with AOX1 methylation.AOX1 methylation interacted with fungi intake (OR=2.06,95％ CI:1.12-3.79) and physical activity (OR=2.18,95％CI:1.16-4.09) synergistically,on the risk for breast cancer,but no additive interaction effects were observed.Non-methylation of IRF4 could increase the risk for breast cancer,with statistical significance (OR=1.71,95％CI:0.99-7.43).Neither multiplication nor additive interactions were observed between IRF4 methylation and environmental factors.Conclusion Non-methylation of AOX1 and IRF4 were a risk factors for breast cancer.

Association between AOX1, IRF4 methylation in peripheral blood leukocyte DNA and the risks of breast cancer: a case-control study / 中华流行病学杂志

Objective To understand the relationship between AOX1,IRF4 gene methylation status in peripheral blood leukocyte DNA,as well as its interaction with environmental factors,and the risk of breast cancer.Methods A case-control study was conducted among 401 breast cancer patients and 555 cancer-free controls selected from 2010 to 2014.Methylation sensitive-high resolution melting curve analysis was used to detect the methylation status of AOX1 and IRF4.The multiplication interaction effect between genes' methylation and environmental factors on the risk of breast cancer was analyzed by using unconditional logistic regression,and Excel software was used to analyze the additive interaction effect.Results Individuals without AOX1 methylation had a 1.37-fold (95％ CI:1.02-1.84) higher breast cancer risk compared to individuals with AOX1 methylation.AOX1 methylation interacted with fungi intake (OR=2.06,95％ CI:1.12-3.79) and physical activity (OR=2.18,95％CI:1.16-4.09) synergistically,on the risk for breast cancer,but no additive interaction effects were observed.Non-methylation of IRF4 could increase the risk for breast cancer,with statistical significance (OR=1.71,95％CI:0.99-7.43).Neither multiplication nor additive interactions were observed between IRF4 methylation and environmental factors.Conclusion Non-methylation of AOX1 and IRF4 were a risk factors for breast cancer.

Mechanism for synergistic effect of IRF4 and MITF on tyrosinase promoter / 中南大学学报(医学版)

Objective:To investigate the mechanism for the synergistic effect of interferon regulatory factor 4 (IRF4) and microphthalmia-associated transcription factor (MITF) on tyrosinase (TYR)promoter.Methods:The synergistic transcriptional effect,subcellular localization,and protein-protein interaction for IRF4 and MITF were observed by luciferase assay,immunofluorescence,GST-pull down,and co-immunoprecipitation,respectively.Results:IRF4 and MITF proteins were co-expressed in the cell nucleus.IRF4 augmented the transcriptional function of MITF (but not the mutant MITF) to activate the expression of the TYR promoter,but with no effect on other MITF-specific target promoters.IRF4 alone did not affect TYR promoter significantly.No direct interaction between the two proteins was noted.Conclusion:IRF4 and MITF exert a specifically synergistic effect on activation of TYR promoter through IRF4-mediated upregulation of transcriptional function of MITF.This synergistic effect is mainly regulated by MITF;DNA might be involved in the interaction between the two proteins.

Interferon regulatory factor 4: regulate and control of lymphocyte / 国际儿科学杂志

Interferon regulatory factors(IRF)are key factors in interferon induction. IRF4, a member of the IRF family of transcription factors, is expressed in cells of the immune system where it transducers signals from various receptors to activate or repress gene expression. IRF4 expression is a key regulator for the development T helper cell subsets and B lymphocyte differentiation. A series of recent studies have further demonstrated critical functions for IRF4. This review focuses on the recent advances on roles of IRF4, including infection, autoimmune disease and immune malignancy. A better understanding of IRF4 will hopefully provide new biomark and potentially guide the design of novel therapeutic approaches.