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Background RORγt + Foxp3 + (Th17-like) Tregs are a plastic Treg subset implicated in immune-related diseases; however, the mechanism of Treg phenotypic transformation in malignant pleural effusion (MPE) has not been elucidated. Methods The percentage of CD4 + CD25 + Foxp3 + Helios + and RORγt + Foxp3 + Tregs from peripheral blood and pleural effusion mononuclear cells were measured. The level of interferon regulatory factor 4 (IRF4) mRNA expression was detected by quantitative real-time reverse transcription polymerase chain reaction. The effects of IRF4 on the induction of Tregs from patients with non-small cell lung cancer (NSCLC) were evaluated in vitro. Correlation assays between IRF4 expression and the frequency of RORγt + Foxp3 + Tregs were performed. Results The frequency of CD4 + CD25 + Foxp3 + Helios + Tregs and CD4 + RORγt + Th17 cells was both increased in the MPE of NSCLC patients. The group of double-positive Foxp3 + RORγt + Treg phenotype were identified in the pleural effusion. A significant increase in the frequency of Foxp3 + RORγt + Tregs was found in MPE compared with the non-malignant pleural effusion (NPE). Compared to NPE, the relative level of IRF4 expression was increased in the MPE. IRF4 expression was positively associated with the frequency of Foxp3 + RORγt + Tregs in the PE. In vitro, the level of Helios mRNA and protein expression was reduced in induced Tregs following IRF4 over-expression. Additionally, the level of RORγt protein expression was substantially increased. However, ectopic Helios expression in induced Tregs reversed the effects induced by enhanced IRF4 expression. Conclusion IRF4 may serve as a potential molecule that promotes the conversion of regulatory T cells from MPE to a Th17-like phenotype by modulating Helios.

Background H7N9 avian influenza is an infection of public health concern, in part because of its high mortality rate and pandemic potential. Aims To describe the clinical features of H7N9 avian influenza and the response to treatment. Methods Clinical, radiological and histopathological data, and treatment‐related of H7N9‐infected patients hospitalised during 2014–2017 were extracted and analysed. Results A total of 17 H7N9 patients (three females; mean age, 58.4 ± 13.7 years) was identified; of these six died. All patients presented with fever and productive cough; four patients had haemoptysis and 13 had chest distress and/or shortness of breath. Early subnormal white blood cell count and elevation of serum liver enzymes were common. Multilobar patchy shadows, rapid progression to ground‐glass opacities, air bronchograms and consolidation were the most common imaging findings. Histopathological examination of lung tissue of three patients who died showed severe alveolar epithelial cell damage, with inflammatory exudation into the alveolar space and hyaline membrane formation; widened alveolar septae, prominent inflammatory cell infiltration; and hyperplasia of pneumocytes. Viral inclusions were found in the lung tissue of two patients. All patients received antiviral drugs (oseltamivir ± peramivir). Four patients carried the rs12252‐C/C interferon‐induced transmembrane protein‐3 (IFITM3) genotype, while the others had the C/T genotype. Conclusions H7N9 virus infection causes human influenza‐like symptoms, but may rapidly progress to severe pneumonia and even death. Clinicians should be alert to the possibility of H7N9 infection in high‐risk patients. The presence of the IFITM3 rs12252‐C genotype may predict severe illness.