scholarly journals Cross-talk between Tetraspanin CD9 and Transmembrane Adaptor Protein Non-T Cell Activation Linker (NTAL) in Mast Cell Activation and Chemotaxis

2013 ◽  
Vol 288 (14) ◽  
pp. 9801-9814 ◽  
Author(s):  
Ivana Hálová ◽  
Lubica Dráberová ◽  
Monika Bambousková ◽  
Martin Machyna ◽  
Lucie Stegurová ◽  
...  
Keyword(s):  
Mast Cell ◽  
T Cell ◽  
T Cell Activation ◽  
Cross Talk ◽  
Cell Activation ◽  
Adaptor Protein ◽  
Mast Cell Activation

Enzymatic Treatment of Whey Proteins in Cow’s Milk Results in Differential Inhibition of IgE-Mediated Mast Cell Activation Compared to T-Cell Activation

2012 ◽  
Vol 159 (3) ◽  
pp. 263-270 ◽  
Author(s):  
Karen Knipping ◽  
Betty C.A.M. van Esch ◽  
Adrie G. van Ieperen-van Dijk ◽  
Els van Hoffen ◽  
Ton van Baalen ◽  
...  
Keyword(s):  
Mast Cell ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Whey Proteins ◽  
Enzymatic Treatment ◽  
Mast Cell Activation ◽  
Differential Inhibition ◽  
Ige Mediated

Targeting phosphoinositide 3-kinase δ for allergic asthma

2012 ◽  
Vol 40 (1) ◽  
pp. 240-245 ◽  
Author(s):  
Wendy C. Rowan ◽  
Janet L. Smith ◽  
Karen Affleck ◽  
Augustin Amour
Keyword(s):  
Mast Cell ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Critical Role ◽  
T Cell Response ◽  
Mast Cell Activation ◽  
Th2 Cytokines ◽  
Onset Of Action ◽  
Phosphoinositide 3 Kinase

Chronic inflammation in the lung has long been linked to the pathogenesis of asthma. Central to this airway inflammation is a T-cell response to allergens, with Th2 cytokines driving the differentiation, survival and function of the major inflammatory cells involved in the allergic cascade. PI3Kδ (phosphoinositide 3-kinase δ) is a lipid kinase, expressed predominantly in leucocytes, where it plays a critical role in immune receptor signalling. A selective PI3Kδ inhibitor is predicted to block T-cell activation in the lung, reducing the production of pro-inflammatory Th2 cytokines. PI3Kδ is also involved in B-cell and mast cell activation. Therefore the inhibition of PI3Kδ should dampen down the inflammatory cascade involved in the asthmatic response through a wide breadth of pharmacology. Current anti-inflammatory therapies, which are based on corticosteroids, are effective in controlling inflammation in mild asthmatics, but moderate/severe asthmatic patients remain poorly controlled, experiencing recurrent exacerbations. Corticosteroids have no effect on mast cell degranulation and do not act directly on B-cells, so, overall, a PI3Kδ inhibitor has the potential to deliver improvements in onset of action, efficacy and reduced exacerbations in moderate/severe asthmatics. Additionally, PI3Kδ inhibition is expected to block effects of Th17 cells, which are increasingly implicated in steroid-insensitive asthma.

scholarly journals The Involvement of Protein Kinase D in T Cell-Induced Mast Cell Activation

2016 ◽  
Vol 171 (3-4) ◽  
pp. 203-208 ◽  
Author(s):  
Pazit Salamon ◽  
Irit Shefler ◽  
Alon Y. Hershko ◽  
Yoseph A. Mekori
Keyword(s):  
Mast Cell ◽  
T Cell ◽  
Protein Kinase ◽  
Cell Activation ◽  
Mast Cell Activation ◽  
Protein Kinase D

scholarly journals Cooperative Interaction of Nck and Lck Orchestrates Optimal TCR Signaling

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 834
Author(s):  
Frederike A. Hartl ◽  
Jatuporn Ngoenkam ◽  
Esmeralda Beck-Garcia ◽  
Liz Cerqueira ◽  
Piyamaporn Wipa ◽  
...  
Keyword(s):  
T Cell ◽  
Ligand Binding ◽  
T Cell Activation ◽  
Cell Activation ◽  
Adaptor Protein ◽  
Cooperative Interaction ◽  
Tcr Signaling ◽  
Binding Motifs ◽  
Adaptive Immune

The T cell antigen receptor (TCR) is expressed on T cells, which orchestrate adaptive immune responses. It is composed of the ligand-binding clonotypic TCRαβ heterodimer and the non-covalently bound invariant signal-transducing CD3 complex. Among the CD3 subunits, the CD3ε cytoplasmic tail contains binding motifs for the Src family kinase, Lck, and the adaptor protein, Nck. Lck binds to a receptor kinase (RK) motif and Nck binds to a proline-rich sequence (PRS). Both motifs only become accessible upon ligand binding to the TCR and facilitate the recruitment of Lck and Nck independently of phosphorylation of the TCR. Mutations in each of these motifs cause defects in TCR signaling and T cell activation. Here, we investigated the role of Nck in proximal TCR signaling by silencing both Nck isoforms, Nck1 and Nck2. In the absence of Nck, TCR phosphorylation, ZAP70 recruitment, and ZAP70 phosphorylation was impaired. Mechanistically, this is explained by loss of Lck recruitment to the stimulated TCR in cells lacking Nck. Hence, our data uncover a previously unknown cooperative interaction between Lck and Nck to promote optimal TCR signaling.

scholarly journals MicroRNA-4443 regulates mast cell activation by T cell–derived microvesicles

2018 ◽  
Vol 141 (6) ◽  
pp. 2132-2141.e4 ◽  
Author(s):  
Irit Shefler ◽  
Pazit Salamon ◽  
Francesca Levi-Schaffer ◽  
Adam Mor ◽  
Alon Y. Hershko ◽  
...  
Keyword(s):  
Mast Cell ◽  
T Cell ◽  
Cell Activation ◽  
Mast Cell Activation

The transmembrane adaptor protein NTAL limits mast cell chemotaxis toward prostaglandin E2

2018 ◽  
Vol 11 (556) ◽  
pp. eaao4354 ◽  
Author(s):  
Ivana Halova ◽  
Monika Bambouskova ◽  
Lubica Draberova ◽  
Viktor Bugajev ◽  
Petr Draber
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
T Cell Activation ◽  
Cell Activation ◽  
Adaptor Protein ◽  
Prostaglandin E ◽  
Dependent Manner ◽  
And Function ◽  
Cell Chemotaxis

Chemotaxis of mast cells is one of the crucial steps in their development and function. Non–T cell activation linker (NTAL) is a transmembrane adaptor protein that inhibits the activation of mast cells and B cells in a phosphorylation-dependent manner. Here, we studied the role of NTAL in the migration of mouse mast cells stimulated by prostaglandin E2 (PGE2). Although PGE2 does not induce the tyrosine phosphorylation of NTAL, unlike IgE immune complex antigens, we found that loss of NTAL increased the chemotaxis of mast cells toward PGE2. Stimulation of mast cells that lacked NTAL with PGE2 enhanced the phosphorylation of AKT and the production of phosphatidylinositol 3,4,5-trisphosphate. In resting NTAL-deficient mast cells, phosphorylation of an inhibitory threonine in ERM family proteins accompanied increased activation of β1-containing integrins, which are features often associated with increased invasiveness in tumors. Rescue experiments indicated that only full-length, wild-type NTAL restored the chemotaxis of NTAL-deficient cells toward PGE2. Together, these data suggest that NTAL is a key inhibitor of mast cell chemotaxis toward PGE2, which may act through the RHOA/ERM/β1-integrin and PI3K/AKT axes.

scholarly journals Mast Cells Enhance T Cell Activation: Importance of Mast Cell Costimulatory Molecules and Secreted TNF

2006 ◽  
Vol 176 (4) ◽  
pp. 2238-2248 ◽  
Author(s):  
Susumu Nakae ◽  
Hajime Suto ◽  
Motoyasu Iikura ◽  
Maki Kakurai ◽  
Jonathon D. Sedgwick ◽  
...  
Keyword(s):  
Mast Cell ◽  
T Cell ◽  
Mast Cells ◽  
T Cell Activation ◽  
Cell Activation ◽  
Costimulatory Molecules

scholarly journals Cdc42 Couples T Cell Receptor Endocytosis to GRAF1-Mediated Tubular Invaginations of the Plasma Membrane

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1388 ◽  
Author(s):  
Rossatti ◽  
Ziegler ◽  
Schregle ◽  
Betzler ◽  
Ecker ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
T Cell Activation ◽  
Cell Activation ◽  
Adaptor Protein ◽  
Cell Receptor ◽  
Small Gtpase ◽  
Endocytic Pathway ◽  
Bar Domain ◽  
Endocytic Vesicles

: T cell activation is immediately followed by internalization of the T cell receptor (TCR). TCR endocytosis is required for T cell activation, but the mechanisms supporting removal of TCR from the cell surface remain incompletely understood. Here we report that TCR endocytosis is linked to the clathrin-independent carrier (CLIC) and GPI-enriched endocytic compartments (GEEC) endocytic pathway. We show that unlike the canonical clathrin cargo transferrin or the adaptor protein Lat, internalized TCR accumulates in tubules shaped by the small GTPase Cdc42 and the Bin/amphiphysin/Rvs (BAR) domain containing protein GRAF1 in T cells. Preventing GRAF1-positive tubules to mature into endocytic vesicles by expressing a constitutively active Cdc42 impairs the endocytosis of TCR, while having no consequence on the uptake of transferrin. Together, our data reveal a link between TCR internalization and the CLIC/GEEC endocytic route supported by Cdc42 and GRAF1.

scholarly journals Mast cells enhance T cell activation: Importance of mast cell-derived TNF

2005 ◽  
Vol 102 (18) ◽  
pp. 6467-6472 ◽  
Author(s):  
S. Nakae ◽  
H. Suto ◽  
M. Kakurai ◽  
J. D. Sedgwick ◽  
M. Tsai ◽  
...  
Keyword(s):  
Mast Cell ◽  
T Cell ◽  
Mast Cells ◽  
T Cell Activation ◽  
Cell Activation
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