1.Regulatory T cells and asthma.
Sheng-Tao ZHAO ; Chang-Zheng WANG
Journal of Zhejiang University. Science. B 2018;19(9):663-673
Asthma is a chronic disease of airway inflammation due to excessive T helper cell type 2 (Th2) response. Present treatment based on inhalation of synthetic glucocorticoids can only control Th2-driven chronic eosinophilic inflammation, but cannot change the immune tolerance of the body to external allergens. Regulatory T cells (Tregs) are the main negative regulatory cells of the immune response. Tregs play a great role in regulating allergic, autoimmune, graft-versus-host responses, and other immune responses. In this review, we will discuss the classification and biological characteristics, the established immunomodulatory mechanisms, and the characteristics of induced differentiation of Tregs. We will also discuss the progress of Tregs in the field of asthma. We believe that further studies on the regulatory mechanisms of Tregs will provide better treatments and control strategies for asthma.
Antigens, CD/analysis*
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Apyrase/analysis*
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Asthma/immunology*
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Cell Differentiation
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Cytokines/metabolism*
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Humans
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Lymphocyte Transfusion
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T-Lymphocytes, Regulatory/immunology*
2.Preretinal Neovascularization by Laser-induced Thrombosis in Albino Rats and Inhibition of Neovascularization by Genistein.
Kyu Hyeong PARK ; Jae Jun LEE ; Shin Goo KANG ; Jun Kyo LEE ; Sang Mok LEE ; Jong Hyun KIM ; Young Suk YU ; Jae Heung LEE ; Hum CHUNG
Journal of the Korean Ophthalmological Society 2002;43(12):2555-2564
PURPOSE: To determine the effect of genistein, an inhibitor of protein tyrosine kinase, on preretinal neovascularization through the quantification of retinal neovascularization using image analyzer in an experimental rat model. METHODS: In 36 eyes of 36 rats, retinal vein occlusion was induced by photodynamic therapy with an argon green laser and systemic injection of rose bengal (40 mg/kg). The development and progression of retinal neovascularization was followed weekly by fluorescein angiography. Seven rats were sacrificed each week, after which two eyes were prepared with H and E staining for histologic examination, and five were prepared as a control group using ADPase staining for neovascularization analysis. In the remaining fifteen eyes, retinal vein occlusion was also induced using the same method. Immediately after vein occlusion, 4.0 mg of genistein dissolved in dimethyl sulfoxide (DMSO) was injected intraperitoneally twice a day for the first 7 days. Five rats were sacrificed each week and stained with ADPase. After ADPase staining, those samples with evidence of neovascularization were quantified using an image analyzer. RESULTS: No retinal neovasularizaion was found at the end of the first week. The size of retinal neovascularization for the five eyes sacrificed at the end of week 2 and 3 were 6.53+/-2.11 mm2 and 3.77+/-3.51 mm2 in the control group, and 2.22+/-1.01 mm2 and 1.64+/-0.88 mm2 in the genistein treatment group, respectively. Retinal neovascularization was successfully suppressed until two weeks after laser treatment by genistein in this rat neovascularization model. CONCLUSIONS: Genistein may be a useful treatment modality to suppress retinal neovascularization complicated with retinal ischemic injury.
Animals
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Apyrase
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Argon
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Dimethyl Sulfoxide
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Fluorescein Angiography
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Genistein*
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Models, Animal
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Photochemotherapy
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Protein-Tyrosine Kinases
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Rats*
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Retinal Neovascularization
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Retinal Vein Occlusion
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Retinaldehyde
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Rose Bengal
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Thrombosis*
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Veins
3.P2X and P2Y Receptors Mediate Contraction Induced by Electrical Field Stimulation in Feline Esophageal Smooth Muscle.
Young Rae CHO ; Hyeon Soon JANG ; Won KIM ; Sun Young PARK ; Uy Dong SOHN
The Korean Journal of Physiology and Pharmacology 2010;14(5):311-316
It is well-known that electrical field stimulation (EFS)-induced contraction is mediated by a cholinergic mechanism and other neurotransmitters. NO, ATP, calcitonin gene-related peptide (CGRP), and substance P are released by EFS. To investigate the purinergic mechanism involved in the EFS-induced contraction, purinegic receptors antagonists were used. Suramine, a non-selective P2 receptor antagonist, reduced the contraction induced by EFS. NF023 (10(-7)~10(-4) M), a selective P2X antagonist, inhibited the contraction evoked by EFS. Reactive blue (10(-6)~10(-4) M), selective P2Y antagonist, also blocked the contraction in a dose-dependent manner. In addition, P2X agonist alpha,beta-methylene 5'-adenosine triphosphate (alphabetaMeATP, 10(-7)~10(-5) M) potentiated EFS-induced contraction in a dose-dependent manner. P2Y agonist adenosine 5'-[beta-thio]diphosphate trilithium salt (ADPbetaS, 10(-7)~10(-5) M) also potentiated EFS-induced contractions in a dose-dependent manner. Ecto-ATPase activator apyrase (5 and 10 U/ml) reduced EFS-induced contractions. Inversely, 6-N,N-diethyl-D-beta,gamma-dibromomethylene 5'-triphosphate triammonium (ARL 67156, 10(-4) M) increased EFS-induced contraction. These data suggest that endogenous ATP plays a role in EFS-induced contractions which are mediated through both P2X-receptors and P2Y-receptors stimulation in cat esophageal smooth muscle.
Adenosine
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Adenosine Triphosphatases
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Adenosine Triphosphate
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Animals
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Apyrase
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Calcitonin Gene-Related Peptide
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Calcium
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Cats
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Contracts
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GTP-Binding Proteins
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Muscle, Smooth
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Neurotransmitter Agents
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Polyphosphates
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Substance P
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Suramin
4.Expression levels of co-inhibitory molecules CTLA-4, LAG-3, PD-1 and CD39 on CD4⁺ T cells correlate with progression of non-small cell lung cancer.
Tengfei WEI ; Jun ZHANG ; Yu WU ; Dandan ZHANG ; Longkun LU ; Qian SHEN
Chinese Journal of Oncology 2014;36(6):424-429
OBJECTIVETo detect the expression levels of co-inhibitory molecules, including CTLA-4, LAG-3, PD-1 and CD39, on CD4⁺ T cells in peripheral blood or tumor tissues from NSCLC patients and to investigate their potential internal relationships with the progression of NSCLC.
METHODSEighty-eight patients including 53 NSCLC, 17 disease control cases and 18 healthy controls were studied. All the peripheral blood and 13 cases of tumor and tumor-adjacent tissues from surgically treated NSCLC patients were obtained. The expression levels of co-inhibitory molecules CTLA-4, LAG-3, PD-1 and CD39 were assayed by flow cytometry (FCM).
RESULTSThe ratios of CD4⁺ CTLA-4⁺ T cells, CD4⁺ LAG-3⁺ T cells, CD4⁺ PD-1⁺ T cells and CD4⁺ CD39⁺ T cells in the peripheral blood of NSCLC patients were (2.49 ± 2.43)%, (2.47 ± 3.50)%, (12.94 ± 5.96)% and (6.78 ± 5.21)%, respectively, the ratio of CD4⁺ CTLA-4⁺ T cells was significantly higher in the peripheral blood of NSCLC patients than that in the disease controls and healthy controls (P < 0.05) . The ratio of CD4(+)PD-1⁺ T cells was also highly raised in the peripheral blood of NSCLC patients than that in the healthy controls (P < 0.05). Further stratified analysis indicated that the ratio of CD4⁺ PD-1⁺ T cells was (13.21 ± 5.96)% in NSCLC patients entering stages III and IV, also significantly increased as compared with that of (11.06 ± 3.42)% in the patients undergoing stages I and II (P < 0.05). More CD4⁺ CTLA-4⁺ T cells, CD4⁺ LAG-3⁺ T cells and CD4⁺ PD-1⁺ T cells were verified in the cancer tissues (5.07 ± 2.11)%, (7.86 ± 3.24)% and (40.20 ± 18.84)%, respectively, than those in their matched peripheral blood (3.13 ± 1.01)%, (2.65 ± 1.48)% and (15.79 ± 5.69)%, (P < 0.05 for all), and especially, CD4⁺ CTLA-4⁺ T cells and CD4⁺ PD-1⁺ T cells were also highly increased than those in matched cancer-adjacent tissues (P < 0.05 for all).
CONCLUSIONSThe increased expression levels of co-inhibitory molecules CTLA-4, LAG-3 and PD-1 on CD4⁺ T cells in peripheral blood and tumor tissues may be one of the mechanisms related to immune escape of tumor cells, acceleration of disease progression and poor prognosis in NSCLC patients.
Antigens, CD ; metabolism ; Apyrase ; metabolism ; CD4-Positive T-Lymphocytes ; metabolism ; CTLA-4 Antigen ; metabolism ; Carcinoma, Non-Small-Cell Lung ; diagnosis ; metabolism ; Disease Progression ; Flow Cytometry ; Humans ; Lung Neoplasms ; diagnosis ; metabolism ; Programmed Cell Death 1 Receptor ; metabolism
5.Morphological Changes of Astrocytes and Muller Cells in the Neonatal Rat Model of Retinopathy of Prematurity.
Hoo Jae HANN ; Young Hwa KIM ; Hee Lai LEE
Korean Journal of Anatomy 2002;35(1):53-64
OBJECTIVES: Retinopathy of prematurity (ROP) is one of the major cause of vision loss among children. Recently, the prevalence of ROP is markedly increasing as the survival rate of very-low-birth-weight premature infants has been improved. It is widely accepted that retinal hypoxia results in the release of factors influencing new blood vessel growth. But, it is little known about the morphological changes of retinal astrocytes and Muller cells in the ROP model. So, we planned to investigate the morphological changes of those retinal glial cells induced by alternating hyperoxic and hypoxic injury in ROP. METHODS: Newborn rats (postnatal day 6) were exposed to two different oxygen concentrations alternating every 24 hours until postnatal day 14. Used oxygen concentrations were 10~15% for hypoxic episode and 55~80% for hyperoxic episode. Afterthen, they were returned to room air. A group of animal served as a room air control. Retinal vascularity was assessed by ADPase reaction and morphology of retinal glial cells was observed using transmisson electron microscope. RESULTS: Preretinal neovascular tufts were observed in 2 out of 12 animals of group III (75/10%) and 4 out of 12 animals of group IV (80/10%), respectively. There was no remarkable structural change of astrocytes. But we could observe some morphological changes of Muller cells. Retraction of the radial processes of Muller cells and breaking of basal lamina were noted at the site of preretinal neovascularization. Decrease in the space occupied by the cytoplasmic processes of Muller cells was observed in the inner nuclear layer of group IV retinae. Infiltration of microglia or macrophage into the vitreo-retinal interface and the site of extravasation was noted. Findings suggestive of neuronal cell death were also observed especially in the inner nuclear layer. CONCLUSIONS: Morphological change of Muller cells and resultant loss of integrity of internal limiting membrane seemed to be the most important step for preretinal neovascularization. But, no structural changes of astrocytes were noted.
Animals
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Anoxia
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Apyrase
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Astrocytes*
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Basement Membrane
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Blood Vessels
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Cell Death
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Child
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Cytoplasm
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Ependymoglial Cells*
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Humans
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Infant, Newborn
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Infant, Premature
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Macrophages
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Membranes
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Microglia
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Models, Animal*
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Neuroglia
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Neurons
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Oxygen
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Prevalence
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Rats*
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Retina
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Retinaldehyde
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Retinopathy of Prematurity*
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Survival Rate