Downregulation of lncRNA XIST may promote Th17 differentiation through KDM6A-TSAd pathway in neuromyelitis optica spectrum disorders.

BACKGROUNDS: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease with significant female preponderance. X inactive specific transcript (XIST) is a long non-coding RNA (lncRNA) and a key regulator of X-chromosome inactivation which is related to the sex-bias of autoimmunity. And Th17 cell proportion was significantly elevated in NMOSD according to our previous study. OBJECTIVES: This study aimed to explore the expression levels of lncRNA XIST-KDM6A-TSAd pathway in lymphocytes of female NMOSD patients, and investigate its possible relationship with pathogenesis of NMOSD. METHODS AND RESULTS: The study enrolled 30 acute-phase untreated female NMOSD patients and 30 age-matched female healthy controls, their lymphocytes were collected for experiments. Microarray as well as validation experiments showed lncRNA XIST was significantly downregulated in the NMOSD group. And the levels of lysine demethylase 6A (KDM6A) decreased in NMOSD and showed significant positive correlation with XIST. The levels of T cell-specific adapter (TSAd) mRNA and protein levels were significantly lower in NMOSD. And Chromatin immunoprecipitation assay demonstrated that NMOSD had more H3K27me3 modification than control at TSAd promoter region. CONCLUSIONS: The present study introduced a potential pathway that following lncRNA XIST downregulation, which process may promote Th17 differentiation in NMOSD. These findings shed new light on the immune regulation mechanism about lncRNA XIST and related epigenetic features, which may contribute to develop female-specific treatment plans.

Regulatory T cell activity in immunosuppresive mice model of pseudomonas aeruginosa pneumonia.

Pseudomonas aeruginosa (PA) pneumonia is a refractory, even lethal complication in immunosuppressive individuals and immune disturbances may promote the pathological process. We aimed to investigate the regulatory T (Treg) cell activity in an immunosuppressive mice model of PA pneumonia by estimating levels of main transcription factor and the main effector of Treg cells, i.e., Forkhead box protein 3 (FOXP3) and interleukine-10 (IL-10). Seventy-two BALB/c mice were divided into four groups randomly: control (A), PA pneumonia (B), immunosuppression (C) and immunosuppression with PA pneumonia (D). Mice were sacrificed at 4, 8 and 24 h after establishing experimental models. The pathological changes of lung tissue were graded, and the FOXP3 mRNA and serum IL-10 levels were detected. Histological analysis of lung tissues showed there were no significantly pathological changes in groups A and C, but significantly pathological changes were found in groups B and D, especially in group D at 8 h (P<0.05). The expression levels of FOXP3 mRNA in groups A and C showed no significant changes at the three time points, which were significantly lower than those in groups B and D (P<0.05). FOXP3 mRNA levels were lowest at 4 h, and there was significant difference between groups B and D (P<0.05). The serum levels of IL-10 in groups A and C were almost normal at the three time points, but decreased significantly in groups B and D (P<0.05). The serum levels of IL-10 decreased to the lowest at 8 h, especially in group D (P<0.05). The results indicate that PA pneumonia in immunosuppressive individuals worsens rapidly, which may be associated with Treg cells function disturbance. And Treg cells may be promising as adjuvant therapeutics for PA pneumonia in immunosuppressive individuals.

Pulmonary embolism, deep vein thrombosis and recurrent bone cysts in a patient with hypereosinophilic syndrome.

Herein we present a case of hypereosinophilic syndrome with a unique clinical presentation. A 32-year-old man was admitted because of fever, hemoptysis and chest pain. The main clinical features include hypereosinophilia, deep vein thrombosis, pulmonary embolism, thrombocytopenia and recurrent bone cysts. The plain film of the left foot revealed dissolvent bone destruction. The histological findings of bone cysts include eosinophilic infiltration and tissue necrosis. According to the case history and literature, it is possible that hypereosinophilia itself may be a risk for thrombogenesis and the bone destruction.