Humans ; Nerve Tissue Proteins ; Epithelial-Mesenchymal Transition/genetics* ; Constriction, Pathologic ; Receptors, Immunologic ; Epithelial Cells/metabolism* ; Smad3 Protein/metabolism* ; Transforming Growth Factor beta1/metabolism*

Cytokine-activated T cells (CATs) can be easily expanded and are widely applied to cancer immunotherapy. However, the good efficacy of CATs is rarely reported in clinical applications because CATs have no or very low antigen specificity. The low-efficacy problem can be resolved using T cell antigen receptor-engineered CAT (TCR-CAT). Herein, we demonstrate that NY-ESO-1 HLA-A*02:01-specific high-affinity TCR (HAT)-transduced CATs can specifically kill cancer cells with good efficacy. With low micromolar range dissociation equilibrium constants, HAT-transduced CATs showed good specificity with no off-target killing. Furthermore, the high-affinity TCR-CATs delivered significantly better activation and cytotoxicity than the equivalent TCR-engineered T cells (TCR-Ts) in terms of interferon-γ and granzyme B production and in vitro cancer cell killing ability. TCR-CAT may be a very good alternative to the expensive TCR-T, which is considered an effective personalized cyto-immunotherapy.
Cell Line, Tumor ; Cytokines ; metabolism ; Cytotoxicity, Immunologic ; Genetic Engineering ; HLA-A2 Antigen ; metabolism ; Humans ; Immunotherapy, Adoptive ; methods ; Lymphocyte Activation ; Receptors, Antigen, T-Cell ; genetics ; immunology ; T-Lymphocytes ; immunology

OBJECTIVE: To identify differentially expressed genes in peripheral blood mononuclear cells between patients with continuous mild-to-moderate asthma and healthy controls using mRNA microarray in order to explore the underlying signaling pathways and clarify the roles of CD4+ T cells in the pathogenesis of asthma. METHODS: Global transcriptomic profiles of the CD4+ T cells were defined by using Agilent Sure Print G3 Human GE 8×60K microarray. Enrichment pathways were analyzed with Ingenuity Pathway Analysis (IPA) software. RESULTS: Compared with controls, 805 genes were up-regulated, 192 were down-regulated in asthma patients. Among these, the expression of 38 annotated genes have varied by 4 times or more. Expression of CD300A was inversely proportional to the absolute value of eosinophils (r=-0.89, P=0.02) as well as the proportion of eosinophils (r=-0.94, P=0.004), while CSF1R was inversely proportional to PD20 (r=-0.83, P=0.04) and AQLQ (r=-0.88, P=0.02) by correlation analysis. CONCLUSION Numerous pathophysiological pathways may be involved in the pathogenesis of asthma. Above findings have provided a basis for the delineation the pathogenesis of asthma.
Antigens, CD ; genetics ; Asthma ; immunology ; CD4-Positive T-Lymphocytes ; cytology ; Case-Control Studies ; Eosinophils ; Gene Expression Profiling ; Humans ; Leukocytes, Mononuclear ; Oligonucleotide Array Sequence Analysis ; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor ; genetics ; Receptors, Immunologic ; genetics ; Transcriptome

OBJECTIVE: To investigate the expression of leukocyte immunoglobulin-like receptor A3 (LILRA3) in CD14 monocytes of patients with rheumatoid arthritis (RA). METHODS: Fifty three RA patients admitted in the Second Affiliated Hospital of Zhejiang University School of Medicine from February 2017 to August 2017, and 21 healthy subjects were enrolled in the study. The expression of LILRA3 in CD14 monocyte subset was determined by flow cytometry, and its correlations with clinical features, laboratory examination results, antibodies and disease activity were analyzed. RESULTS: LILRA3 percentage in the CD14 monocyte subset of RA patients was higher than that in the healthy controls (<0.01). The percentage of LILRA3 was positively correlated with number of tenderness joints, number of swollen joints and erythrocyte sedimentation rate (=0.280, 0.371, 0.341, <0.05 or <0.01), but was not correlated with the age, course of disease, Sharp score, C reactive protein, blood routine index and immunoglobulin (all >0.05). In addition, the percentages of LILRA3 in the monocytes of rheumatoid factor (RF)-positive or anti-cyclic citrullinated peptide (CCP) antibody-positive patients were significantly higher than those of the RF-or anti-CCP antibody-negative patients (all < 0.05); and the percentage of LILRA3 in patients with DAS28>5.1 was higher than that in patients with DAS28 ≤ 5.1 (<0.05). CONCLUSIONS The expression of LILRA3 is up-regulated in CD14 monocyte subset isolated from RA patients, and it is correlated with disease activity.
Arthritis, Rheumatoid ; blood ; physiopathology ; Autoantibodies ; blood ; Biomarkers ; blood ; Flow Cytometry ; Humans ; Monocytes ; metabolism ; Receptors, Immunologic ; genetics ; Up-Regulation

OBJECTIVETo study the role of triggering receptor expressed on myeloid cells-1(TREM-1) in the pathogenesis of Kawasaki disease (KD).

METHODSBased on color Doppler examination results, 45 children with KD were classified into two groups: coronary artery lesions (CAL group) and no coronary artery lesions (NCAL group). Fifteen children with fever caused by respiratory infection (fever control group) and fifteen healthy children (normal control group) served as controls. Real-time fluorescence quantitative PCR was used to detect the expression of TREM-1 mRNA and DNAX-activating protein 12 (DAP12) mRNA in peripheral blood mononuclear cells (PBMC). ELISA was used to detect the expression of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), DAP12, monocyte chemoattractant protein-1(MCP-1), interleukin-8 (IL-8) proteins levels.

RESULTSThe mean serum protein concentrations of sTREM-1 and DAP12 and the expression levels of TREM-1 mRNA and DAP12 mRNA in PBMC in 45 children with KD (KD group) were significantly higher than in the two control groups (P<0.05). The levels of sTREM-1 protein and TREM-1 mRNA in the CAL subgroup were significantly higher than in the NCAL subgroup (P<0.05). The serum protein concentrations of MCP-1 and IL-8 in the KD group were significantly higher than in the two control groups (P<0.05). The MCP-1 protein level in the CAL subgroup was significantly higher than in the NCAL subgroup (P<0.05). In children with KD, there was a positive correlation between serum sTREM-1 and MCP-1 levels (r=0.523, P<0.05).

CONCLUSIONSTREM-1 activation may be involved in the development of KD.

Chemokine CCL2 ; blood ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Interleukin-8 ; blood ; Male ; Membrane Glycoproteins ; blood ; genetics ; physiology ; Mucocutaneous Lymph Node Syndrome ; etiology ; immunology ; RNA, Messenger ; analysis ; Receptors, Immunologic ; blood ; genetics ; physiology ; Triggering Receptor Expressed on Myeloid Cells-1

OBJECTIVETo investigate the effect of triggering receptor expressed on myeloid cells 2 (TREM-2) overexpression on airway inflammation and remodeling in mice with asthma.

METHODSA total of 40 BALB/c mice were randomly divided into normal control, asthma, empty vector, and TREM-2 overexpression groups (n=10 each). Ovalbumin (OVA) sensitization and challenge were performed to establish the model of asthma. The mice in the control group were given normal saline, and those in the empty vector and TREM-2 overexpression groups were transfected with adenovirus vector and TREM-2 adenovirus, respectively. RT-PCR and Western blot were used to measure the expression of TREM-2, MMP-2, MMP-9, ADAM33, and ADAM8. Bronchoalveolar lavage fluid (BALF) was collected to perform cell counting and classification. ELISA was used to measure the total serum level of IgE and the levels of cytokines in BALF.

RESULTSCompared with the control group, the asthma group showed significant reductions in the mRNA and protein expression of TREM-2 (P<0.05), a significantly increased level of Th2 cytokine (P<0.05), and significantly increased numbers of total cells and classified cells. Compared with the asthma group, the TREM-2 overexpression group showed a significantly reduced level of Th2 cytokine (P<0.05), a significantly reduced level of IgE (P<0.05), and significantly reduced numbers of total cells and classified cells (P<0.05), as well as significantly downregulated expression of the inflammatory factors and growth factors MMP-2, MMP-9, TGF-β1, ADAM8, and ADAM33 (P<0.05).

CONCLUSIONSTREM-2 overexpression significantly alleviates airway inflammation and airway remodeling in mice with asthma and may become a potential target for the prevention and treatment of childhood asthma.

Airway Remodeling ; Animals ; Asthma ; etiology ; immunology ; Cytokines ; analysis ; Female ; Membrane Glycoproteins ; genetics ; physiology ; Mice ; Mice, Inbred BALB C ; Ovalbumin ; immunology ; RNA, Messenger ; analysis ; Receptors, Immunologic ; genetics ; physiology

Developmental dyslexia in children is one of the neurodevelopmental disorders and is affected by various susceptible genes. In recent years, researchers have found some susceptible genes for dyslexia via chromosome analysis, genome-wide association studies, association analysis, gene function research, neuroimaging, and neurophysiological techniques. This article reviews the research advances in susceptible genes for developmental dyslexia, and with the study on susceptible genes for dyslexia, it lays a foundation for in-depth studies on the "gene-brain-behavior" level and provides scientific clues for exploring etiology and pathogenesis of dyslexia.
Child ; Dyslexia ; genetics ; Forkhead Transcription Factors ; genetics ; Genetic Predisposition to Disease ; Humans ; Microtubule-Associated Proteins ; genetics ; Nerve Tissue Proteins ; genetics ; Nuclear Proteins ; genetics ; Receptors, Immunologic ; genetics

The object of this review is to help readers to understand meta-analysis of genetic association study. Genetic association studies are a powerful approach to identify susceptibility genes for common diseases. However, the results of these studies are not consistently reproducible. In order to overcome the limitations of individual studies, larger sample sizes or meta-analysis is required. Meta-analysis is a statistical tool for combining results of different studies on the same topic, thus increasing statistical strength and precision. Meta-analysis of genetic association studies combines the results from independent studies, explores the sources of heterogeneity, and identifies subgroups associated with the factor of interest. Meta-analysis of genetic association studies is an effective tool for garnering a greater understanding of complex diseases and potentially provides new insights into gene-disease associations.
Arthritis, Rheumatoid/genetics/pathology ; Databases, Factual ; *Genetic Association Studies ; Genotype ; Humans ; Polymorphism, Single Nucleotide ; Receptors, Immunologic/genetics

OBJECTIVETo explore the change of RAGE-NF-κB signaling pathway during the course of hyperoxia-induced lung injury in newborn rats, and the effect of glucocorticoid on this pathway.

METHODSTwenty-four Sprague-Dawley neonatal rats were randomly divided into three groups (n=8 each) : sham control (control group), hyperoxia-induced acute lung injury (model group) and glucocorticoid-treated acute lung injury (glucocorticoid group). Rats were sacrificed at 13 days after birth. RAGE and NF-κB expression levels in lung tissues were detected by reverse transcription polymerase chain reaction, Western blot and immunohistochemistry analysis. The levels of tumor necrosis factor α (TNF-α) and sRAGE in bronchoalveolar lavage fluid (BALF) and serum were measured using ELISA. Lung damage was evaluated by histological examinations.

RESULTSRAGE and NF-κB mRNA and protein expression levels in lung tissues were significantly increased in the model and glucocorticoid groups compared with the control group (P<0.05). Serum RAGE concentrations were significantly increased but RAGE concentrations in BALF were significantly reduced in the model and glucocorticoid groups compared with the control group (P<0.05). RAGE and NF-κB expression at both mRNA and protein levels in lung tissues was significantly lower in the glucocorticoid group than in the model group (P<0.05). RAGE concentrations were significantly lower in serum (P<0.05), but were higher in BALF (P<0.05) in the glucocorticoid group than in the model group.

CONCLUSIONSRAGE-NF-κB pathway plays an important role in hyperoxia-induced lung injury in neonatal rats, and glucocorticoid administration may play a protective role against the lung injury by down-regulating RAGE-NF-κB signaling pathway.

Animals ; Animals, Newborn ; Glucocorticoids ; pharmacology ; Hyperoxia ; complications ; Lung Injury ; prevention & control ; NF-kappa B ; analysis ; genetics ; physiology ; Rats ; Rats, Sprague-Dawley ; Receptor for Advanced Glycation End Products ; Receptors, Immunologic ; analysis ; genetics ; physiology ; Signal Transduction ; drug effects ; Tumor Necrosis Factor-alpha ; analysis

OBJECTIVETo investigate lipopolysaccharide (LPS)-induced changes of cytoskeletal filamentous actin in primary isolated pulmonary microvascular endothelial cells (PMVECs) from wild-type and RAGE knock-out mouse.

METHODSThe lungs of wild-type and RAGE knock-out mice were digested with collagenase type I to obtain endothelial cells purified by anti-CD31-coupled magnetic beads. The PMVEC identified by factor VIII labeling were stimulated with LPS at different concentrations and the changes of filamentous actin were observed by confocal microscopy.

RESULTSThe cultured primary cells showed typical endothelial cell phenotype as examined with factor VIII labeling. LPS stimulation caused rearrangement of the cytoskeletal filament F-actin in wild-type mouse PMVECs with stress fiber formation, but such changes were not obvious in RAGE knock-out mouse PMVECs.

CONCLUSIONMouse PMVECs of a high purity can be obtained by immune magnetic beads. RAGE is involved in LPS-induced destruction of mouse PMVEC cytoskeletons.

Actins ; metabolism ; Animals ; Cells, Cultured ; Cytoskeleton ; metabolism ; Endothelial Cells ; cytology ; Lipopolysaccharides ; Lung ; cytology ; Mice ; Mice, Knockout ; Microvessels ; cytology ; Phenotype ; Receptor for Advanced Glycation End Products ; Receptors, Immunologic ; genetics ; metabolism