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Anne-Christine Thierry

Bio: Anne-Christine Thierry is an academic researcher. The author has contributed to research in topics: Chemokine receptor & C-C chemokine receptor type 7. The author has an hindex of 5, co-authored 5 publications receiving 101 citations.

Papers
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Journal ArticleDOI
TL;DR: Findings indicate that PDE4 inhibitors can affect T cell responses by acting at the DC level and may increase the understanding of the therapeutic implication of PDE 4 inhibitors for T(h)1-mediated disorders.
Abstract: Inhibitors of cAMP-specific phosphodiesterase (PDE) 4 have been shown to inhibit inflammatory mediator release and T cell proliferation, and are considered candidate therapies for T(h)1-mediated diseases. However, little is known about how PDE4 inhibitors influence dendritic cells (DC), the cells responsible for the priming of naive T(h) cells. Therefore, we investigated the PDE profile of monocyte-derived DC, and whether PDE4 inhibitors modulate DC cytokine production and T cell-polarizing capacity. We mainly found cAMP-specific PDE4 enzymatic activity in both immature and mature DC. In contrast to monocytes that mainly express PDE4B, we found that PDE4A is the predominant PDE4 subtype present in DC. Immature DC showed reduced ability to produce IL-12p70 and tumor necrosis factor (TNF)-alpha upon lipopolysaccharide or CD40 ligand (CD40L) stimulation in the presence of PDE4 inhibitors, whereas cytokine production upon CD40L stimulation of fully mature DC in the presence of PDE4 inhibitors was not affected. Exposure to PDE4 inhibitors for 2 days during DC maturation did not influence T cell-stimulatory capacity or acquisition of a mature phenotype, but increased the expression of the chemokine receptor CXCR4. Furthermore, DC matured in the presence of PDE4 inhibitors showed reduced capacity to produce IL-12p70 and TNF-alpha upon subsequent CD40L stimulation. Using these PDE4 inhibitor-matured DC to stimulate naive T cells resulted in a reduction of IFN-gamma-producing (T(h)1) cells. These findings indicate that PDE4 inhibitors can affect T cell responses by acting at the DC level and may increase our understanding of the therapeutic implication of PDE4 inhibitors for T(h)1-mediated disorders.

66 citations

Journal Article
TL;DR: It is demonstrated that fluorescent synthetic chemokines constitute promising ligands for the development of chemokine receptor-binding assays on intact cells, for applications such as cell-based, high throughput screening, and studies of chemoksine receptor expression by primary cells.
Abstract: Chemokines constitute a protein family that exhibit a variety of biological activities involved in normal and pathological physiological processes. CCL11 (eotaxin), CCL19 (MIP-3beta), CCL22 (MDC), CXCL11 (I-TAC) and CXCL12 (SDF-1alpha) chemokines, modified with the Alexa Fluor 647 fluorescent dye at specific positions along their sequence, were produced by a chemical route and their biological activities were characterized. In a migration assay, fluorescent chemokines were as biologically active as the unmodified forms. All labeled chemokines specifically stained cell lines transfected with the appropriate human chemokine receptors. The specificity of binding was further established by showing that the unlabeled ligands efficiently competed with the labeled chemokines for binding to their respective receptor. A low molecular weight antagonist of CXCR4 prevented binding of labeled CXCL12 to CXCR4 comparably to a neutralizing anti-CXCR4 antibody. Finally, labeled CCL19 was used for the staining of primary cells, illustrating that this reagent can be used for studying CCR7 expression on different cell types. Together, these results demonstrate that fluorescent synthetic chemokines constitute promising ligands for the development of chemokine receptor-binding assays on intact cells, for applications such as cell-based, high throughput screening, and studies of chemokine receptor expression by primary cells.

11 citations

Journal ArticleDOI
TL;DR: The total chemical synthesis of chemokines is undertaken, which has successfully produced over 30 chemokine species, which exhibit biological activities similar to, or greater than, those reported by others.

10 citations

Journal ArticleDOI
09 Dec 2004-Vaccine
TL;DR: It is indicated that the rE1 glycoprotein could constitute a non-replicating rubella vaccine.

9 citations

Journal ArticleDOI
TL;DR: It is exemplified that biotinylated synthetic chemokines constitute promising ligands for the development of chemokine receptor-binding assays on whole cells, provided the position of the biotin moiety introduced along the sequence is adequately chosen.
Abstract: A chemokine binding assay on whole cells was developed using biotinylated synthetic CCL22 as a model ligand. CCL22 analogues were produced by a chemical route, resulting in > 97% homogeneous and defined polypeptides. First, the 5 biotinylated CCL22 analogues synthesized were captured by agarose-immobilized streptavidin, indicating that the biotin molecules introduced in positions G1, K27, K49, K61, and K66 of CCL22 were accessible for binding. Then, it was established using a migration assay that the biotinylated chemokines were at least as biologically active as the unmodified CCL22 form. Subsequently, the biotinylated chemokines were evaluated in an FACS-based whole-cell binding assay. Surprisingly, only the CCL22 analogue with the biotin in position K66 constituted a suitable staining reagent for CCR4-positive cells. Finally, binding characteristics and reproducibility of the binding assay were outlined for the CCL22 analogue with the biotin in position K66. These results exemplified that biotinylated ...

9 citations


Cited by
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Journal ArticleDOI
Peter H. Schafer1
TL;DR: Apremilast is an orally available targeted PDE4 inhibitor that modulates a wide array of inflammatory mediators involved in psoriasis and psoriatic arthritis, including decreases in the expression of inducible nitric oxide synthase, TNF-α, and interleukin (IL)-23 and increases IL-10.

335 citations

Journal ArticleDOI
TL;DR: A number of strategies are currently being pursued in attempts to improve clinical efficacy and reduce side effects, including delivery via the inhaled route, and/or development of non‐emetic PDE4 inhibitors and mixed PDE inhibitors.
Abstract: Phosphodiesterase4 inhibitors are currently under development for the treatment of respiratory diseases including asthma and chronic obstructive pulmonary disease. The rationale for the development of this drug class stems from our understanding of the role of PDE4 in suppressing the function of a range of inflammatory and resident cells thought to contribute toward the pathogenesis of these diseases. Similarly, numerous preclinical in vivo studies have shown that PDE4 inhibitors suppress characteristic features of these diseases, namely, cell recruitment, activation of inflammatory cells and physiological changes in lung function in response to a range of insults to the airways. These potentially beneficial actions of PDE4 inhibitors have been successfully translated in phase II and III clinical trials with roflumilast and cilomilast. However, dose limiting side effects of nausea, diarrhoea and headache have tempered the enthusiasm of this drug class for the treatment of these respiratory diseases. A number of strategies are currently being pursued in attempts to improve clinical efficacy and reduce side effects, including delivery via the inhaled route, and/or development of non-emetic PDE4 inhibitors and mixed PDE inhibitors.

315 citations

01 Jan 2009
TL;DR: Fluorescent ligands, antibodies, autofluorescent proteins as well as the evolving technologies for chemical labeling with peptide- and protein-tags are described and their major applications concerning the GPCR life cycle are presented.
Abstract: The investigation of biological systems highly depends on the possibilities that allow scientists to visualize and quantify biomolecules and their related activities in real-time and non-invasively. Gprotein coupled receptors represent a family of very dynamic and highly regulated transmembrane proteins that are involved in various important physiological processes. Since their localization is not confined to the cell surface they have been a very attractive "moving target" and the understanding of their intracellular pathways as well as the identified protein-protein-interactions has had implications for therapeutic interventions. Recent and ongoing advances in both the establishment of a variety of labeling methods and the improvement of measuring and analyzing instrumentation, have made fluorescence techniques to an indispensable tool for GPCR imaging. The illumination of their complex life cycle, which includes receptor biosynthesis, membrane targeting, ligand binding, signaling, internalization, recycling and degradation, will provide new insights into the relationship between spatial receptor distribution and function. This review covers the existing technologies to track GPCRs in living cells. Fluorescent ligands, antibodies, autofluorescent proteins as well as the evolving technologies for chemical labeling with peptide- and protein-tags are described and their major applications concerning the GPCR life cycle are presented.

243 citations

Journal ArticleDOI
TL;DR: Apremilast, given orally at 20 or 30 mg twice daily, seems to be efficacious, safe, and tolerable for patients with moderate to severe plaque psoriasis, and these results support continuing, longer-term studies.

227 citations

Journal ArticleDOI
TL;DR: An overview of the cyclic AMP axis and its role as a regulator of immune functions is provided and the clinical and translational relevance of interventions with these processes are discussed.
Abstract: Nucleotide signaling molecules contribute to the regulation of cellular pathways. In the immune system, cyclic adenosine monophosphate (cAMP) is well established as a potent regulator of innate and adaptive immune cell functions. Therapeutic strategies to interrupt or enhance cAMP generation or effects have immunoregulatory potential in autoimmune and inflammatory disorders. Here, we provide an overview of the cyclic AMP axis and its role as a regulator of immune functions and discuss the clinical and translational relevance of interventions with these processes.

195 citations