scholarly journals Exosomes Derived From Heat Stroke Cases Carry miRNAs Associated With Inflammation and Coagulation Cascade

2020 ◽  
Author(s):  
Yue Li ◽  
Qiang Wen ◽  
Huaisheng Chen ◽  
Xinhui Wu ◽  
Bin Liu ◽  
...  
Keyword(s):  
T Cell ◽  
Inflammatory Response ◽  
Healthy Volunteers ◽  
Signaling Pathway ◽  
Platelet Activation ◽  
Intercellular Communication ◽  
Heat Stroke ◽  
Cell Receptor ◽  
Coagulation Cascade ◽  
Cell Receptor Signaling

Abstract Background: The pathological mechanism of HS is associated with the dysbalanced inflammation and coagulation cascade. The cells-derived circulating extracellular vesicles (EVs) as a novel pathway mediating intercellular communication were evidenced to be associated with immune response and inflammation in critical inflammatory syndromes such as sepsis. Despite previous studies demonstrating that these vesicles contain genetic material related to their biological function, their molecular cargo during heat stroke is relatively unknown. In this study, we evaluated the presence of microRNAs (miRNAs) and messenger RNAs (mRNAs) related to inflammatory response and coagulation cascade in exosomes of patients with heat stroke. Methods: Blood samples were collected from 3 patients with heat stroke at ICU admission. Three healthy volunteers were used as control subjects. Exosomes were isolated by ultracentrifugation, their miRNA content was profiled by next generation sequencing and mRNA content was evaluated by qRT-PCR array. Results: As compared with healthy volunteers, exosomes from patients with heat stroke had significant changes in 202 exosomal miRNAs (154 miRNAs upregulated and 48 downregulated). The most upregulated miRNAs included miR-511-3p, miR-122-5p, miR-155-3p, miR-1290 and let7-5p whileas the most downregulated ones included miR-150-3p, 146a-5p and 151a-3p. The GO enrichment by the miRNAs of patients with heat stroke compared with control subjects were related mostly to inflammatory response including T cell activation, B cell receptor signaling, DC chemotaxis and leukocyte migration, and platelet activation and blood coagulation. KEGG pathway analysis determined those identified miRNAs were mainly enriched to the signal transduction pathways namely, T cell receptor signaling pathway, Ras signaling pathway, Chemokine signaling pathway, Platelet activation, and Leukocyte transendothelial migration. These pathways were mainly related to inflammation and hemostasis. Multiple targeted mRNAs associated with the inflammatory response, blood coagulation and platelet activation were further verified in serum exosomes.Conclusions: Exosomes from patients with heat stroke convey miRNAs and mRNAs related to pathogenic pathways, including inflammatory response and coagulation cascade. Exosomes may represent a novel mechanism for intercellular communication during heat stroke.

scholarly journals Exosomes Derived From Heat Stroke Cases Carry miRNAs Associated With Inflammation and Coagulation Cascade

2021 ◽  
Vol 12 ◽  
Author(s):  
Yue Li ◽  
Qiang Wen ◽  
Huaisheng Chen ◽  
Xinhui Wu ◽  
Bin Liu ◽  
...  
Keyword(s):  
T Cell ◽  
Inflammatory Response ◽  
Healthy Volunteers ◽  
Blood Coagulation ◽  
Platelet Activation ◽  
Intercellular Communication ◽  
Heat Stroke ◽  
Cell Receptor ◽  
Coagulation Cascade ◽  
Cell Receptor Signaling

The pathological mechanism underlying heat stroke (HS) is associated with the dysbalanced inflammation and coagulation cascade. Cell-derived circulating extracellular vesicles (EVs), as a novel pathway mediating intercellular communication, are associated with the immune response and inflammation in critical inflammatory syndromes, such as sepsis. Although these vesicles contain genetic material correlated with their biological function, their molecular cargo during HS remains unknown. In this study, we evaluate the presence of microRNAs (miRNAs) and messenger RNAs (mRNAs) associated with inflammatory responses and coagulation cascade in exosomes of patients with HS. Blood samples were collected from three patients with HS at the time of admission to the intensive care unit; three healthy volunteers were selected as control. Exosomes were isolated using ultracentrifugation, and their miRNA content was profiled using next-generation sequencing; mRNA content was evaluated using qPCR array. Compared with those from healthy volunteers, exosomes from patients with HS showed substantial changes in the expression of 202 exosomal miRNAs (154 upregulated and 48 downregulated miRNAs). The most upregulated miRNAs included miR-511-3p, miR-122-5p, miR-155-3p, miR-1290, and let7-5p, whereas the most downregulated ones included miR-150-3p, 146a-5p, and 151a-3p. Gene ontology enrichment of the miRNAs of patients with HS compared with control subjects were associated mostly with inflammatory response, including T cell activation, B cell receptor signaling, dendritic cell chemotaxis and leukocyte migration, and platelet activation and blood coagulation. The identified miRNAs were primarily enriched to the signal transduction pathways namely, T cell receptor signaling, Ras signaling, chemokine signaling, platelet activation, and leukocyte transendothelial migration, all of which are associated with inflammation and hemostasis. Multiple targeted mRNAs associated with the inflammatory response, blood coagulation, and platelet activation were further verified in serum exosomes. Exosomes from patients with HS convey miRNAs and mRNAs associated with pathogenic pathways, including inflammatory response and coagulation cascade. Exosomes may represent a novel mechanism for intercellular communication during HS.

scholarly journals The CARMA1-Bcl10 Signaling Complex Selectively Regulates JNK2 Kinase in the T Cell Receptor-Signaling Pathway

Immunity ◽  
2007 ◽  
Vol 26 (1) ◽  
pp. 55-66 ◽  
Author(s):  
Marzenna Blonska ◽  
Bhanu P. Pappu ◽  
Reiko Matsumoto ◽  
Hongxiu Li ◽  
Bing Su ◽  
...  
Keyword(s):  
T Cell ◽  
Signaling Pathway ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Receptor Signaling ◽  
Signaling Complex ◽  
T Cell Receptor Signaling ◽  
Receptor Signaling Pathway ◽  
Cell Receptor Signaling

The Expression of T Cell Receptor Signaling Genes Is Associated with Poor Response to IFN-α and/or PUVA in Mycosis Fungoides.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2053-2053
Author(s):  
Magdalena Wozniak ◽  
Pablo Ortiz ◽  
Lorraine Tracey ◽  
Jose L. Peralto ◽  
Monica Alvarez ◽  
...  
Keyword(s):  
T Cell ◽  
Signaling Pathway ◽  
Mycosis Fungoides ◽  
T Cell Receptor ◽  
Cell Lymphoma ◽  
Cell Receptor ◽  
T Cell Lymphoma ◽  
Cutaneous T Cell Lymphoma ◽  
T Cell Receptor Signaling ◽  
Cell Receptor Signaling

Abstract Mycosis fungoides (MF) is a low-grade cutaneous T-cell lymphoma, in which malignant T cell clones (mostly CD4+) arise in the skin from the early disease stages. IFN-α is widely used in the treatment of MF and when used in combination with PUVA has been reported as an effective treatment, with overall response rates of 30%–80%, and complete response rates of 14%–25%. However, up to date there is no information available on prognostic factors that could help to predict response to IFN-α /PUVA in MF. The purpose of the study was to find the molecular signature associated with IFN-α /PUVA resistance, or lack of remission after IFN-α /PUVA treatment. The gene expression profile of the pre-treatment samples from 30 MF patients enrolled in a random clinical trial with IFN-α and/or PUVA has been analyzed by use of cDNA microarrays. Following the treatment outcome, the patients have been divided into good responders (23 patients that have achieved complete remission in the time of 24 weeks or less) and bad responders (7 patients that have not reached completed remission or have shown progression of the disease during treatment). The genes associated with good vs. bad response have been identified. Four genes associated with cell cycle regulation and tumour microenviroment have been identified to predict good response by the significance analysis of microarrays (SAM) correlating expression data with survival time. Moreover, 38 genes involved in T cell receptor signaling pathway, NF-kB activation and Jak-Stat signaling pathway have been found to be associated with unfavorable response to treatment by use of SAM analysis. This was validated using other bioinformatics tools based on t-statistics and Cox-model, applying False Discovery Rate for multiple testing. Furthermore, using a web-based tool (Signs) that uses a combination of gene filtering, clustering and survival model building, a 2-gene model has been obtained. This model could distinguish two groups of MF patients with probability of remission at 24 weeks of 15%, and 60% (log-rank test, p:0.007). This confirms that TCR-signaling plays a key role in cutaneous T-cell lymphoma cell survival; and could potentially be used for stratifying MF patients treated with IFN-α /PUVA into different risk-groups, if confirmed in additional studies.

Structure and function of Tec family kinase Itk

2011 ◽  
Vol 2 (3) ◽  
pp. 223-232
Author(s):  
Qian Qi ◽  
Arun Kumar Kannan ◽  
Avery August
Keyword(s):  
T Cell ◽  
Signaling Pathway ◽  
Cell Receptor ◽  
T Cell Receptor Signaling ◽  
Receptor Signaling Pathway ◽  
Tec Family Kinase ◽  
And Function ◽  
Th2 Differentiation ◽  
Potential Use ◽  
Cell Receptor Signaling

AbstractItk is a member of the Tec family of kinases that is expressed predominantly in T cells. Itk regulates the T cell receptor signaling pathway to modulate T cell development and T helper cell differentiation, particularly Th2 differentiation. Itk is also important for the development and function of iNKT cells. In this review we discuss current progress on our understanding of the structure, activation and signaling pathway of Itk, in addition to inhibitors that have been developed, which target this kinase. We also place in context the function of Itk, available inhibitors and potential use in treating disease.

scholarly journals T cell receptor signaling pathway and cytokine-cytokine receptor interaction affect the rehabilitation process after respiratory syncytial virus infection

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7089 ◽  
Author(s):  
Zuanhao Qian ◽  
Zhenglei Zhang ◽  
Yingying Wang
Keyword(s):  
T Cell ◽  
Signaling Pathway ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Cytokine Receptor ◽  
Receptor Interaction ◽  
T Cell Receptor Signaling ◽  
Rsv Infection ◽  
Receptor Signaling Pathway ◽  
Cell Receptor Signaling

Background Respiratory syncytial virus (RSV) is the main cause of respiratory tract infection, which seriously threatens the health and life of children. This study is conducted to reveal the rehabilitation mechanisms of RSV infection. Methods E-MTAB-5195 dataset was downloaded from EBI ArrayExpress database, including 39 acute phase samples in the acute phase of infection and 21 samples in the recovery period. Using the limma package, differentially expressed RNAs (DE-RNAs) were analyzed. The significant modules were identified using WGCNA package, and the mRNAs in them were conducted with enrichment analysis using DAVID tool. Afterwards, co-expression network for the RNAs involved in the significant modules was built by Cytoscape software. Additionally, RSV-correlated pathways were searched from Comparative Toxicogenomics Database, and then the pathway network was constructed. Results There were 2,489 DE-RNAs between the two groups, including 2,386 DE-mRNAs and 103 DE-lncRNAs. The RNAs in the black, salmon, blue, tan and turquoise modules correlated with stage were taken as RNA set1. Meanwhile, the RNAs in brown, blue, magenta and pink modules related to disease severity were defined as RNA set2. In the pathway networks, CD40LG and RASGRP1 co-expressed with LINC00891/LINC00526/LINC01215 were involved in the T cell receptor signaling pathway, and IL1B, IL1R2, IL18, and IL18R1 co-expressed with BAIAP2-AS1/CRNDE/LINC01503/SMIM25 were implicated in cytokine-cytokine receptor interaction. Conclusion LINC00891/LINC00526/LINC01215 co-expressed with CD40LG and RASGRP1 might affect the rehabilitation process of RSV infection through the T cell receptor signaling pathway. Besides, BAIAP2-AS1/CRNDE/LINC01503/SMIM25 co-expressed with IL1 and IL18 families might function in the clearance process after RSV infection via cytokine-cytokine receptor interaction.

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