T Cell Adhesion Primes Antigen Receptor-Induced Calcium Responses through a Transient Rise in Adenosine 3′,5′-Cyclic Monophosphate

Conche, Claire; Boulla, Geneviève; Trautmann, Alain; Randriamampita, Clotilde

doi:10.1016/j.immuni.2008.10.020

Cited by 49 publications

(60 citation statements)

References 41 publications

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“…Indeed, the adhesive signal delivered by LFA1 (induced to adopt its high-affinity form through chemokine-dependent signaling) has been shown to be sufficient to induce immunological synapse formation, whereas the TCR signal is important for synapse stabilization and for sustained activation (Contento et al, 2010). In contrast, we have recently reported that T cell adhesion is able to prime the T cell response, regardless of whether integrins were involved (Conche et al, 2009). Finally, T cells have been shown to be able to sense the rigidity of the object with which they interact.…”

Section: Discussionmentioning

confidence: 99%

“…We have excluded the involvement of a Ca 2+ rise. We have recently shown that a very early transient increase in cAMP is triggered in T lymphocytes after contact with APCs (Conche et al, 2009). This cAMP transient could constitute a good candidate for adhesion-induced antisynapse formation.…”

Section: Discussionmentioning

confidence: 99%

“…Although the immunological synapse was initially reported to form after antigen recognition, antigenindependent contact can also trigger the formation of such a structure (Revy et al, 2001). More recently, the activation of LFA1 (a leukocyte integrin composed of ITGB2 and ITGAL) alone upon T cell contact with an APC has been shown to promote the establishment of T cell polarity, preparing the T cell for antigen recognition (Contento et al, 2010), supporting the idea that T cell adhesion can prime the subsequent T cell receptor (TCR) response (Conche et al, 2009).…”

Section: Introductionmentioning

confidence: 95%

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T cell adhesion triggers an early signaling pole distal to the immune synapse

Guedj

Abraham

Jullié

et al. 2016

Journal of Cell Science

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The immunological synapse forms at the interface between a T cell and an antigen-presenting cell after foreign antigen recognition. The immunological synapse is considered to be the site where the signaling cascade leading to T lymphocyte activation is triggered. Here, we show that another signaling region can be detected before formation of the synapse at the opposite pole of the T cell. This structure appears during the first minute after the contact forms, is transient and contains all the classic components that have been previously described at the immunological synapse. Its formation is independent of antigen recognition but is driven by adhesion itself. It constitutes a reservoir of signaling molecules that are potentially ready to be sent to the immunological synapse through a microtubuledependent pathway. The antisynapse can thus be considered as a pre-synapse that is triggered independently of antigen recognition.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

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T cell adhesion triggers an early signaling pole distal to the immune synapse

Guedj

Abraham

Jullié

et al. 2016

Journal of Cell Science

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“…Эта модель согласуется с противовоспалительными эффектами cAMP, которые показаны в некоторых других клеточных системах [38,39] и предположением, что ингибирование продукции cAMP должно усиливать Т-клеточный иммунитет. Однако результаты некоторых недавних исследований показали, что продукция cAMP может так же стимулировать Т-клеточный ответ [40].…”

Section: рисунокunclassified

Imiquimod: the biochemical mechanisms of immunomodulatory and anti-inflammatory activity

et al. 2013

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Imidazoquinolins represent a new group of compounds that recently entered into clinical practice as anti-tumor and anti-viral immune modulators. They are low molecular weight synthetic guanosine-like molecules. Although imiquimod, the most widely used imidazoquinolin, is recommended for the treatment of several forms of skin cancer and papillomas, the molecular mechanisms of its action are not fully understood. In particular, imiquimod has been characterized as a specific agonist of Toll-like receptor 7 (TLR7) and is widely used in this capacity in a large number of experimental studies and clinical trials. However, detailed analysis of the published data with the use of imiquimod, suggests that its biological activity can not be explained only by interaction with TLR7. There are indications of a direct interaction of imiquimod with adenosine receptors and other molecules that regulate the synthesis of cyclic adenosine monophosphate. A detailed understanding of the biochemical basis of imiquimod immunomodulating and antitumor effect will increase its clinical effectiveness and accelerate the development of new drugs with similar but improved medical properties. This review summarizes the published data concerning the effects of imiquimod on a variety of intracellular biochemical processes and signaling pathways.

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“…In a few cases increased cAMP may even potentiate the T-cell activation signal (15), particularly at early stages of activation. Recent MS-based proteomic studies have been useful in characterizing changes in the phosphoproteome of T cells under various stimuli such as T-cell receptor stimulation (16), prostaglandin signaling (17), and oxidative stress (18), so much of the total Jurkat phosphoproteome is known.…”

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confidence: 99%

Analyses of PDE-regulated phosphoproteomes reveal unique and specific cAMP-signaling modules in T cells

Beltejar

Lau

Golkowski

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Specific functions for different cyclic nucleotide phosphodiesterases (PDEs) have not yet been identified in most cell types. Conventional approaches to study PDE function typically rely on measurements of global cAMP, general increases in cAMP-dependent protein kinase (PKA), or the activity of exchange protein activated by cAMP (EPAC). Although newer approaches using subcellularly targeted FRET reporter sensors have helped define more compartmentalized regulation of cAMP, PKA, and EPAC, they have limited ability to link this regulation to downstream effector molecules and biological functions. To address this problem, we have begun to use an unbiased mass spectrometry-based approach coupled with treatment using PDE isozyme-selective inhibitors to characterize the phosphoproteomes of the functional pools of cAMP/PKA/EPAC that are regulated by specific cAMP-PDEs (the PDE-regulated phosphoproteomes). In Jurkat cells we find multiple, distinct PDE-regulated phosphoproteomes that can be defined by their responses to different PDE inhibitors. We also find that little phosphorylation occurs unless at least two different PDEs are concurrently inhibited in these cells. Moreover, bioinformatics analyses of these phosphoproteomes provide insight into the unique functional roles, mechanisms of action, and synergistic relationships among the different PDEs that coordinate cAMP-signaling cascades in these cells. The data strongly suggest that the phosphorylation of many different substrates contributes to cAMP-dependent regulation of these cells. The findings further suggest that the approach of using selective, inhibitor-dependent phosphoproteome analysis can provide a generalized methodology for understanding the roles of different PDEs in the regulation of cyclic nucleotide signaling.

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T Cell Adhesion Primes Antigen Receptor-Induced Calcium Responses through a Transient Rise in Adenosine 3′,5′-Cyclic Monophosphate

Cited by 49 publications

References 41 publications

T cell adhesion triggers an early signaling pole distal to the immune synapse

T cell adhesion triggers an early signaling pole distal to the immune synapse

Imiquimod: the biochemical mechanisms of immunomodulatory and anti-inflammatory activity

Analyses of PDE-regulated phosphoproteomes reveal unique and specific cAMP-signaling modules in T cells

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