1047 Extracellular matrix of glioblastoma inhibits polarization and transmigration of T cells: a role of tenascin-c in immune suppression

2009 ◽  
Vol 7 (2) ◽  
pp. 100
Author(s):  
J. Huang ◽  
Y. Cheng ◽  
Y. Lin ◽  
H. Lin ◽  
C. Su ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
T Cells ◽  
Immune Suppression ◽  
Tenascin C

scholarly journals Extracellular Matrix of Glioblastoma Inhibits Polarization and Transmigration of T Cells: The Role of Tenascin-C in Immune Suppression

2010 ◽  
Vol 185 (3) ◽  
pp. 1450-1459 ◽  
Author(s):  
Jyun-Yuan Huang ◽  
Yu-Jung Cheng ◽  
Yu-Ping Lin ◽  
Huan-Ching Lin ◽  
Chung-Chen Su ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
T Cells ◽  
Immune Suppression ◽  
Tenascin C

Platelets enhance CD4+ lymphocyte adhesion to extracellular matrix under flow conditions: Role of platelet aggregation, integrins, and non-integrin receptors

2006 ◽  
Vol 95 (05) ◽  
pp. 815-821 ◽  
Author(s):  
Yuri Vitkovsky ◽  
Grigory Brill ◽  
Alexander Koltakov ◽  
Nahid Farzam ◽  
David Varon ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
T Cells ◽  
Cell Adhesion ◽  
Platelet Aggregation ◽  
T Cell ◽  
Static Condition ◽  
Flow Conditions ◽  
Lymphocyte Adhesion ◽  
Cd4 Lymphocyte

SummaryThe purpose of this study was to examine the role of platelets in CD4+ T lymphocyte adhesion to subendothelial extracellular matrix (ECM). Herpesvirus saimiri (HVS)-infected CD4+ T cells were incubated on ECM. An image analysis was used to evaluate T cell adhesion. Under static condition, T cell activation with 4-α-Phorbol 12-myristate 13-acetate (PMA) resulted in a 2.6-fold increase in cell adhesion. However, adhesion was not affected by platelets. In contrast, under flow (200s−1), platelets markedly enhanced both resting and PMA-activatedT cell adhesion (33- and 48-fold), forming lymphocyte-platelet co-aggregates that contain approximately 90% of the adherent T cells. Abrogation of platelet aggregation with tirofiban inhibited formation of platelet-T cell co-aggregates under flow and reduced T cell adhesion by 74%. Separate and combined blockade of CD40L and P-selectin glycoprotein-1 (PSGL-1) on PMA-activated lymphocytes reduced adhesion under flow in the presence of platelets by 28%, 33%, and 55%, respectively. Blockade of β1-integrins decreased adhesion under both static and flow conditions (by 35% and 44%, respectively), while blockade of β2-integrin reduced adhesion only under static condition (by 23%). A similar adhesion pattern was observed using CD4+ T cells isolated from normal donor peripheral blood. In conclusion, platelets support CD4+ lymphocyte adhesion to ECM under flow by formation of heterotypic platelet-lymphocyte co-aggregates involving αIIbβ3 integrin and β1-related integrins, as well as CD40L and PSGL-1.

scholarly journals The role of extracellular matrix in mouse and human corneal neovascularization

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
M. Barbariga ◽  
F. Vallone ◽  
E. Mosca ◽  
F. Bignami ◽  
C. Magagnotti ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Medical Condition ◽  
Corneal Stroma ◽  
Acanthamoeba Keratitis ◽  
Corneal Neovascularization ◽  
Collagen Vi ◽  
Tenascin C ◽  
Human Proteins ◽  
Specific Proteins

Abstract Corneal neo-vascularization (CNV) is a highly prevalent medical condition which impairs visual acuity. The role of specific proteins in modulating CNV has been extensively reported, although no studies have described the entire human proteome in CNV corneas. In this paper, we performed a proteomic analysis of vascularized vs healthy corneal stroma, in a CNV mouse model and in CNV-affected patients, with a specific focus on extracellular matrix (ECM) proteins. We identified and quantified 2315 murine proteins, 691 human proteins and validated 5 proteins which are differentially expressed in vascularized samples and conserved in mice and humans: tenascin-C and fibronectin-1 were upregulated, while decorin, lumican and collagen-VI were downregulated in CNV samples. Interestingly, among CNV patients, those affected with Acanthamoeba keratitis showed the highest levels of fibronectin-1 and tenascin-C, suggesting a specific role of these two proteins in Acanthamoeba driven corneal CNV. On a broader picture, our findings support the hypothesis that the corneal stroma in CNV samples is disorganized and less compact. We are confident that the dissection of the human corneal proteome may shed new light on the complex pathophysiology of human CNV, and finally lead to improved treatments.

Immunomodulatory role of the extracellular matrix protein tenascin-C in neuroinflammation

2019 ◽  
Vol 47 (6) ◽  
pp. 1651-1660 ◽  
Author(s):  
Susanne Wiemann ◽  
Jacqueline Reinhard ◽  
Andreas Faissner
Keyword(s):  
Extracellular Matrix ◽  
Intracellular Signaling ◽  
Matrix Protein ◽  
Dynamic Network ◽  
Adaptor Proteins ◽  
Extracellular Matrix Protein ◽  
Tenascin C ◽  
Pathological Conditions ◽  
Main Components

The extracellular matrix (ECM) consists of a dynamic network of various macromolecules that are synthesized and released by surrounding cells into the intercellular space. Glycoproteins, proteoglycans and fibrillar proteins are main components of the ECM. In addition to general functions such as structure and stability, the ECM controls several cellular signaling pathways. In this context, ECM molecules have a profound influence on intracellular signaling as receptor-, adhesion- and adaptor-proteins. Due to its various functions, the ECM is essential in the healthy organism, but also under pathological conditions. ECM constituents are part of the glial scar, which is formed in several neurodegenerative diseases that are accompanied by the activation and infiltration of glia as well as immune cells. Remodeling of the ECM modulates the release of pro- and anti-inflammatory cytokines affecting the fate of immune, glial and neuronal cells. Tenascin-C is an ECM glycoprotein that is expressed during embryonic central nervous system (CNS) development. In adults it is present at lower levels but reappears under pathological conditions such as in brain tumors, following injury and in neurodegenerative disorders and is highly associated with glial reactivity as well as scar formation. As a key modulator of the immune response during neurodegeneration in the CNS, tenascin-C is highlighted in this mini-review.

scholarly journals Comprehensive analysis of expression, prognosis and immune infiltration for TIMPs in glioblastoma

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jinkun Han ◽  
Yajun Jing ◽  
Fubing Han ◽  
Peng Sun
Keyword(s):  
Extracellular Matrix ◽  
T Cells ◽  
Cell Signalling ◽  
Treatment Modalities ◽  
Expression Levels ◽  
Immune Infiltration ◽  
Multiple Treatment ◽  
Tissue Inhibitors Of Metalloproteinase ◽  
Timp Family

Abstract Background Tissue inhibitors of metalloproteinase (TIMP) family proteins are peptidases involved in extracellular matrix (ECM) degradation. Various diseases are related to TIMPs, and the primary reason is that TIMPs can indirectly regulate remodelling of the ECM and cell signalling by regulating matrix metalloproteinase (MMP) activity. However, the link between TIMPs and glioblastoma (GBM) is unclear. Objective This study aimed to explore the role of TIMP expression and immune infiltration in GBM. Methods Oncomine, GEPIA, OSgbm, LinkedOmics, STRING, GeneMANIA, Enrichr, and TIMER were used to conduct differential expression, prognosis, and immune infiltration analyses of TIMPs in GBM. Results All members of the TIMP family had significantly higher expression levels in GBM. High TIMP3 expression correlated with better overall survival (OS) and disease-specific survival (DSS) in GBM patients. TIMP4 was associated with a long OS in GBM patients. We found a positive relationship between TIMP3 and TIMP4, identifying gene sets with similar or opposite expression directions to those in GBM patients. TIMPs and associated genes are mainly associated with extracellular matrix organization and involve proteoglycan pathways in cancer. The expression levels of TIMPs in GBM correlate with the infiltration of various immune cells, including CD4+ T cells, macrophages, neutrophils, B cells, CD8+ T cells, and dendritic cells. Conclusions Our study inspires new ideas for the role of TIMPs in GBM and provides new directions for multiple treatment modalities, including immunotherapy, in GBM.

scholarly journals CD73-mediated adenosine production by CD8 T cell-derived extracellular vesicles constitutes an intrinsic mechanism of immune suppression

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Enja Schneider ◽  
Riekje Winzer ◽  
Anne Rissiek ◽  
Isabell Ricklefs ◽  
Catherine Meyer-Schwesinger ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Extracellular Vesicles ◽  
T Cell Activation ◽  
Immune Suppression ◽  
Cell Activation ◽  
Immune Cell ◽  
Dependent Manner ◽  
Intrinsic Mechanism

AbstractImmune cells at sites of inflammation are continuously activated by local antigens and cytokines, and regulatory mechanisms must be enacted to control inflammation. The stepwise hydrolysis of extracellular ATP by ectonucleotidases CD39 and CD73 generates adenosine, a potent immune suppressor. Here we report that human effector CD8 T cells contribute to adenosine production by releasing CD73-containing extracellular vesicles upon activation. These extracellular vesicles have AMPase activity, and the resulting adenosine mediates immune suppression independently of regulatory T cells. In addition, we show that extracellular vesicles isolated from the synovial fluid of patients with juvenile idiopathic arthritis contribute to T cell suppression in a CD73-dependent manner. Our results suggest that the generation of adenosine upon T cell activation is an intrinsic mechanism of human effector T cells that complements regulatory T cell-mediated suppression in the inflamed tissue. Finally, our data underscore the role of immune cell-derived extracellular vesicles in the control of immune responses.

Platelets Enhance CD4+ Lymphocyte Adhesion to Extracellular Matrix under Flow Conditions: Role of Integrins, CD40 Ligand and P-Selectin Glycoprotein Ligand-1.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2656-2656
Author(s):  
Naphtali Savion ◽  
Alexey Solpov ◽  
Boris Shenkman ◽  
Grigory Brill ◽  
Yuri Vitkovsky ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
T Cells ◽  
T Cell ◽  
Cluster Formation ◽  
Cd40 Ligand ◽  
Flow Conditions ◽  
Lymphocyte Adhesion ◽  
Cd4 Lymphocyte ◽  
Static Conditions

Abstract Recent studies established that platelets, beside their haemostatic function play a role in inflammation, immunity and atherosclerosis. In this study, we investigated the role of platelets in CD4+ lymphocyte adhesion to the subendothelial extracellular matrix (ECM) under static and flow conditions. Cultured clone of CD4+ lymphocyte (HVS infected clone) was incubated for 30 min at 37°C under static or flow conditions on tissue culture plates pre-coated with ECM, in the presence or absence of gel-filtered platelets. In separate experiments, the ECM plates were further coated with platelet-poor (PPP) or platelet-rich plasma (PRP) prior to the addition of cells. Flow conditions were applied using the Cone and Plate(let) Analyzer (CPA) device and the results were evaluated by an image analysis system and expressed as the number of adhered T-cells per mm2. Under static conditions, activation of T-cells with phorbol 12-myristate 13-acetate (PMA) led to 2.6-fold increase in cell adhesion. In the presence of platelets the adhesion rate did not change. In contrast, under flow condition (200 s−1), platelets substantially enhanced both resting and PMA-activated T-cells adhesion (12.7- and 18.5-fold, respectively). Moreover, under flow, platelet-T-cell heterotypic clusters appeared on the ECM as revealed by both light and scanning electron microscopy. When ECM was pre-coated with PPP, adhesion of T-cells was enhanced by 2.3- and 1.8-fold under static and flow conditions, respectively. Pre-coating with PRP did not change T-cells adhesion under static but further enhanced T-cells adhesion under flow (by 80% vs. PPP). In this case platelet-lymphocyte clusters were not observed. Similar pattern of results was seen with natural blood-derived CD4+ lymphocytes cultured for 7 days. In these natural T-cells the adhesion under both static and flow conditions was platelet dependent, however, higher adhesion under flow compared to static conditions (55-fold) due to relatively low T-cells adhesion under static conditions and to the heterotypic cluster formation occurring only under flow conditions was observed. We further investigated the role of different receptors in T-cell-platelet cluster formation on ECM. Blockade of β1-dependent integrins on T-cells was followed by a decrease in adhesion under both static and flow conditions in the presence of platelets (by 37% and 43%, respectively). Combined blockade of CD40 ligand (CD40L) and P-selectin glycoprotein ligand-1 (PSGL-1) receptors on the T-cells decreased their adhesion in the presence of platelets by 72% under high shear (600 s−1) but not under low shear (200 s−1) and under static conditions. Blockage of the platelet integrin αIIbβ3 by tirofiban markedly reduced cluster formation thereby decreasing T-cells adhesion (by 90%) under flow conditions. The results of this study show that platelets support CD4+ lymphocyte adhesion to ECM under flow conditions by formation of heterotypic clusters that are dependent on platelet adhesion and aggregation and mediated by CD40L, PSGL-1 and β1-dependent integrins.

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