ABSTRACT
The pathological hallmarks of psoriasis involve alterations in T cell genes associated with transcriptional levels, which are determined by chromatin accessibility. However, to what extent these alterations in T cell transcriptional levels recapitulate the epigenetic features of psoriasis remains unknown. Here, we systematically profiled chromatin accessibility on Th1, Th2, Th1-17, Th17, and Treg cells and found that chromatin remodeling contributes significantly to the pathogenesis of the disease. The chromatin remodeling tendency of different subtypes of Th cells were relatively consistent. Next, we profiled chromatin accessibility and transcriptional dynamics on memory Th/Treg cells. In the memory Th cells, 803 increased and 545 decreased chromatin-accessible regions were identified. In the memory Treg cells, 713 increased and 1206 decreased chromatin-accessible regions were identified. A total of 54 and 53 genes were differentially expressed in the peaks associated with the memory Th and Treg cells. FOSL1, SPI1, ATF3, NFKB1, RUNX, ETV4, ERG, FLI1, and ETC1 were identified as regulators in the development of psoriasis. The transcriptional regulatory network showed that NFKB1 and RELA were highly connected and central to the network. NFKB1 regulated the genes of CCL3, CXCL2, and IL1RN. Our results provided candidate transcription factors and a foundational framework of the regulomes of the disease.
Subject(s)
Humans , Chromatin/genetics , Chromatin Assembly and Disassembly , Gene Regulatory Networks , Psoriasis/genetics , T-Lymphocytes, RegulatoryABSTRACT
Objective To explore the in vitro culture methods for oriented differentiation of peritoneal cells and bone marrow cells into high-purity mast cells,and to identify the function of these mast cells.Methods Peritoneal cells and bone marrow cells were isolated from the peritoneal cavity lavages and femur of C57BL/6 mice,and cultured with both interleukin-3 (IL-3) and stem cell factor for 2 and 4 weeks respectively.Light microscopy was performed to observe the morphology of these cells,toluidine blue staining to identify the degree of maturity of these mast cells,and flow cytometry to measure the expression of cell surface markers C D 117 and FceR Ⅰ α.After the stimulation with compound 48/80 at different concentrations,the degranulation rate of mast cells was counted under the microscope,and β-hexosaminidase release rate was measured by spectrophotometry.Results After 2-or 4-week culture,the mouse peritoneal and bone marrow cells all manifested as refractive suspension cells of uniform size.Toluidine blue staining showed violaceous metachromatic granules in the cytoplasm of the two kinds of cells.The proportions of CD117 or FcεR Ⅰ α single-positive peritoneal and bone marrow-derived mast cells were all more than 95％,and the proportions of CD117/FcεR Ⅰ α double-positive peritoneal and bone marrow-derived mast cells were 97.68％ ± 0.80％ and 96.12％ ± 0.76％ respectively.The degranulation rates of mast cells in the 100-and 1 000-mg/L compound 48/80 groups significantly differed from those in the blank control group (all P ＜ 0.01).Compared with the blank control group,the β-hexosaminidase release rates significantly increased in bone marrow-derived mast cells in the 100-mg/L compound 48/80 group and peritoneal mast cells in the 10-and 100-mg/L compound 48/80 groups (P ＜ 0.01 or 0.05).Conclusion IL-3 and stem cell factor can co-induce the directed differentiation and proliferation of mouse bone marrow stem cells and peritoneal cells,so as to harvest highnuritv mature degranulated mast cells,and lay a foundation for subsequent cell biology research.
ABSTRACT
Objective To measure the levels of plasma D-dimer,activated coagulation factor Ⅶ (FⅦa) and activated clotting factor Ⅻ (FⅫa) in patients with chronic urticaria (CU),and to investigate their relationship with the occurrence of CU.Methods Venous blood samples were collected from 50 patients with CU and 50 healthy human controls.Dry-column immune scattering chromatography was performed to detect the plasma level of D-dimer,and enzyme-linked immunosorbent assay (ELISA) to measure the levels of FⅦa and FⅫa.In addition,autologous plasma skin test (APST) was conducted in 43 patients with CU,and autologous serum skin test (ASST) in 41 patients with CU.A correlation analysis was carried out between the above three parameters and disease severity as well as between the results of APST and ASST and plasma level of D-dimer.Results The levels of plasma D-dimer and F Ⅶa were significantly higher in patients with CU than in healthy human controls (both P ＜ 0.05),while no significant difference was found in FⅫa level between the two groups (P ＞ 0.05).Moreover,the degree of increase in D-dimer plasma level was positively correlated with disease severity in the patients with CU.The plasma level of D-dimer was significantly higher in APST-positive patients than in APST-negative patients (P ＜ 0.05),but not significantly different between ASST-positive and-negative patients (P ＞ 0.05).Conclusions Coagulation mechanism,especially the extrinsic coagulation pathway,is related to the occurrence of CU.Studies on coagulation mechanism are beneficial to the evaluation of severity,and clinical treatment,of CU.
ABSTRACT
An 82-year-old Chinese woman presented with skin eruptions on the thigh and abdomen accompanied by intermittent fever of unknown origin for more than 2 months.No hepatosplenomegaly,lymphadenopathy or neurological abnormality was found with physical examination.There were irregular,tender,indurated,dark-erythematous plaques on bilateral thigh and lower abdomen.along with nonpitting edema and peau d'orange appearance.A significant decrease was observed in the count of white blood cells,red blood cells and platelets,but the serum level of lactate dehydrogenase was elevated.Tumor aspiration and the first pathology yielded no confirmed diagnosis,and the patient had ever been diagnosed with chronic lymphangitis,allergic cutaneous vasculitis and fever of unknown origin in other hospitals.Antibiotic therapy leaded to no improvement,and the lesions gradually spread from the migh to lower abdomen.The second histopathology revealed the presence of atypical lymphoid cells with hyperchromatic nuclei and irregular morphology in the lumens of small blood vessels in subcutaneous tissue.Immunohistochemically,the atypical lymphoid cells were positive for lymphocytotoxic antibody (LCA),CD20,CD790t and bcl-2,but negative for bcl-6,CD10,CD3,CD45RO,CD30,EMA,AEI/3 or CK and vascular endothelial cells were positive for CD34.The diagnosis of intravascular large B-cell lymphoma was made based on the hisstopathological features and immunohistochemical findings.The patient died in two months.
ABSTRACT
A gram-negative bacillus was isolated from the bodies of dead clams among clambanks along the south beach of Jiangsu province. It was confirmed to the Vibrio furnissii by morphological and biochemical characteristic examinations. This isolate grows well in clam's body fluid media and may multiply rapidly in sea-water at temperature about 25—37℃. It is of high toxicity. The healthy clams were all diseased with the same syndrome and died as natural illness by inoculate them with the isolate. It is considered that the large enormous death of clams along the south beach of Jiansu province is concerned with the wide spreading of the clam's infectious disease caused by Vibrio furnissii which hasn't been reported both internal and abroad.