scholarly journals Glycogen synthase kinase 3 (GSK-3) controls T-cell motility and interactions with antigen presenting cells

2019 ◽  
Author(s):  
Alison Taylor ◽  
Christopher E. Rudd
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Motility ◽  
Glycogen Synthase ◽  
Antigen Presenting Cells ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Serine Kinase ◽  
Multiple Substrates ◽  
Antigen Presenting

Abstract Objective: The threonine/serine kinase glycogen synthase kinase 3 (GSK-3) targets multiple substrates in T-cells, regulating the expression of Tbet and PD-1 on T-cells. However, it has been unclear whether GSK-3 can affect the motility of T-cells and their interactions with antigen presenting cells. Results: Here, we show that GSK-3 can regulate T-cell motility. Inhibition of GSK-3, by small molecule SB415286, reduced T-cell motility in terms of distance and displacement. Although SB415286 reduced the number of contacts, the dwell times of established contacts did not differ between T-cells treated with SB415286. These data indicate show that the inhibition of GSK-3 can influence the motility of T-cells and interactions with other cells without affecting the dwell times of cells that make productive contacts.

scholarly journals Glycogen synthase kinase 3 (GSK-3) controls T-cell motility and interactions with antigen presenting cells

2019 ◽  
Author(s):  
Alison Taylor ◽  
Christopher E. Rudd
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Motility ◽  
Glycogen Synthase ◽  
Antigen Presenting Cells ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Serine Kinase ◽  
Multiple Substrates ◽  
Antigen Presenting

Abstract Objective: The threonine/serine kinase glycogen synthase kinase 3 (GSK-3) targets multiple substrates in T-cells, regulating the expression of Tbet and PD-1 on T-cells. However, it has been unclear whether GSK-3 can affect the motility of T-cells and their interactions with antigen presenting cells. Results: Here, we show that GSK-3 can regulate T-cell motility. Inhibition of GSK-3, by small molecule SB415286, reduced T-cell motility in terms of distance and displacement. Although SB415286 reduced the number of contacts, the dwell times of established contacts did not differ between T-cells treated with SB415286. These data indicate show that the inhibition of GSK-3 can influence the motility of T-cells and interactions with other cells without affecting the dwell times of cells that make productive contacts.

scholarly journals Glycogen synthase kinase 3 (GSK-3) controls T-cell motility andinteractions with antigen presenting cells

2020 ◽  
Author(s):  
Alison Taylor ◽  
Christopher E. Rudd
Keyword(s):  
T Cell ◽  
Cell Motility ◽  
Glycogen Synthase ◽  
Antigen Presenting Cells ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Negative Effects ◽  
Serine Kinase ◽  
Multiple Substrates ◽  
Antigen Presenting

Abstract Objective: The threonine/serine kinase glycogen synthase kinase 3 (GSK-3) targets multiple substrates in T-cells and regulates the expression of Tbet and PD-1. However, it has been unclear whether GSK-3 has any effect on T-cell motility or their interactions with antigen presenting cells. Results: Here, we show that GSK-3 controls T-cell motilityand interactions with other cells. Inhibition of GSK-3, using structurally distinct inhibitors, reduced T-cell motility in terms of speed and distance travelled. Furthermore, SB415286 reduced the number of cell to cell contacts, however the duration of these established contacts with other cells did not differ in the presence of SB415286. This inhibition of motility did not affect the ability of GSK-3 inhibitors to enhance cytolytic T-cell (CTL) function in killing tumor targets. These data show that the inhibition of GSK-3 has differential effects on T-cell motility and CTL function where the negative effects on cell-cell interactions is overridden by the increased cytolytic potential of CTLs.

scholarly journals Glycogen synthase kinase 3 (GSK-3) controls T-cell motility andinteractions with antigen presenting cells

2020 ◽  
Author(s):  
Alison Taylor ◽  
Christopher E. Rudd
Keyword(s):  
T Cell ◽  
Cell Motility ◽  
Glycogen Synthase ◽  
Antigen Presenting Cells ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Negative Effects ◽  
Serine Kinase ◽  
Multiple Substrates ◽  
Antigen Presenting

Abstract Objective:The threonine/serine kinase glycogen synthase kinase 3 (GSK-3) targets multiple substrates in T-cells and regulates the expression of Tbet and PD-1. However, it has been unclear whether GSK-3 has any effect on T-cell motility or their interactions with antigen presenting cells. Results: Here, we show that GSK-3 controls T-cell motilityand interactions with other cells. Inhibition of GSK-3, using structurally distinct inhibitors, reduced T-cell motility in terms of speed and distance travelled. Furthermore, SB415286 reduced the number of cell to cell contacts, however the duration of these established contacts with other cells did not differ in the presence of SB415286. This inhibition of motility did not affect the ability of GSK-3 inhibitors to enhance cytolytic T-cell (CTL) function in killing tumor targets. These data show that the inhibition of GSK-3 has differential effects on T-cell motility and CTL function where the negative effects on cell-cell interactions is overridden by the increased cytolytic potential of CTLs.

scholarly journals Tcf-1-mediated transcription in T lymphocytes: differential role for glycogen synthase kinase-3 in fibroblasts and T cells

1999 ◽  
Vol 11 (3) ◽  
pp. 317-323 ◽  
Author(s):  
Frank J. T. Staal ◽  
Boudewijn M. T. Burgering ◽  
Marc van de Wetering ◽  
Hans C. Clevers
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3

scholarly journals Pharmacological Inhibition of Glycogen Synthase Kinase 3 Regulates T Cell Development In Vitro

PLoS ONE ◽  
2013 ◽  
Vol 8 (3) ◽  
pp. e58501 ◽  
Author(s):  
Jan-Hendrik Schroeder ◽  
Lewis S. Bell ◽  
Michelle L. Janas ◽  
Martin Turner
Keyword(s):  
T Cell ◽  
Glycogen Synthase ◽  
T Cell Development ◽  
Cell Development ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Pharmacological Inhibition ◽  
Development In Vitro

scholarly journals Development of Stable Chimeric IL-15 for Trans-Presentation by the Antigen Presenting Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Manoj Patidar ◽  
Naveen Yadav ◽  
Sarat K. Dalai
Keyword(s):  
T Cells ◽  
T Cell ◽  
Half Life ◽  
Therapeutic Potential ◽  
Chimeric Protein ◽  
Antigen Presenting Cells ◽  
T Cell Response ◽  
Antigen Presenting

IL-15 is one of the important biologics considered for vaccine adjuvant and treatment of cancer. However, a short half-life and poor bioavailability limit its therapeutic potential. Herein, we have structured IL-15 into a chimeric protein to improve its half-life enabling greater bioavailability for longer periods. We have covalently linked IL-15 with IgG2 base to make the IL-15 a stable chimeric protein, which also increased its serum half-life by 40 fold. The dimeric structure of this kind of IgG based biologics has greater stability, resistance to proteolytic cleavage, and less frequent dosing schedule with minimum dosage for achieving the desired response compared to that of their monomeric forms. The structured chimeric IL-15 naturally forms a dimer, and retains its affinity for binding to its receptor, IL-15Rβ. Moreover, with the focused action of the structured chimeric IL-15, antigen-presenting cells (APC) would transpresent chimeric IL-15 along with antigen to the T cell, that will help the generation of quantitatively and qualitatively better antigen-specific memory T cells. In vitro and in vivo studies demonstrate the biological activity of chimeric IL-15 with respect to its ability to induce IL-15 signaling and modulating CD8+ T cell response in favor of memory generation. Thus, a longer half-life, dimeric nature, and anticipated focused transpresentation by APCs to the T cells will make chimeric IL-15 a super-agonist for memory CD8+ T cell responses.

Abstract 252: Interleukin-27 Signaling Regulates Myeloid Cells Activation in Atherosclerosis

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Iuliia Peshkova ◽  
Aliia Fatkhullina ◽  
Ekaterina Koltsova
Keyword(s):  
T Cells ◽  
T Cell ◽  
Inflammatory Cytokines ◽  
Antigen Presenting Cells ◽  
Atherosclerotic Lesions ◽  
Mediators Of Inflammation ◽  
Antigen Presenting ◽  
Deficient Mice ◽  
Pro Inflammatory Cytokines

Atherosclerosis is a lipid-driven inflammatory disease characterized by the progressive plaque growth in the vessels. Cytokines are important mediators of inflammation and atherosclerosis. While pro-inflammatory cytokines were extensively investigated, little is known about the role of anti-inflammatory cytokines as to their ability to control vascular inflammation. We tested whether immunoregulatory IL-27R signaling is important to control inflammation in mouse models of atherosclerosis. We found that atherosclerosis-prone mice with hematopoietic deficiency of IL-27R ( Ldlr -/- mice reconstituted with bone marrow from Il27ra -/- ) or global deficiency ( Il27ra -/- x Apoe -/- ) developed significantly larger atherosclerotic lesions compared to controls. Atherosclerotic lesions in IL-27R deficient mice contained more CD45 + leukocytes and CD4 + T cells, which produced pro-atherogenic cytokines IL-17A and TNF-α. These cytokines normally suppressed by IL-27, regulated the expression of CCL2 and other chemokines, which in turn led to accumulation of myeloid CD11b + and CD11c + cells in atherosclerotic aortas. Using two-photon microscopy, we found enhanced interactions between antigen presenting cells and T cells in the aortas of IL-27R deficient mice accompanied by enhanced CD4 T cell proliferation. Moreover, macrophages in Il27ra -/- aortas also demonstrated enhanced ability to produce pro-inflammatory cytokines, including IL-1. The blockade of IL-1R signaling, however, strongly suppressed atherosclerosis progression in IL-27R deficient but not control mice, suggesting an important role of IL-27 in the regulation of IL-1 production in atherosclerosis. Overall, our data demonstrate that IL-27R signaling in atherosclerosis is required to control function of antigen presenting cells modulating subsequent T cell activation in the aortas. Moreover, it controls macrophage activation and pro-inflammatory myeloid cell-derived cytokine production. These mechanisms altogether curb pathogenic T cell lineage differentiation and, thus, atherosclerosis, suggesting potent anti-atherogenic role of IL-27.

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