5 results on '"Coulon, Séverine"'
Search Results
2. Polymeric IgA1 controls erythroblast proliferation and accelerates erythropoiesis recovery in anemia.
- Author
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Coulon, Séverine, Dussiot, Michaël, Grapton, Damien, Maciel, Thiago Trovati, Wang, Pamella Huey Mei, Callens, Celine, Tiwari, Meetu Kaushik, Agarwal, Saurabh, Fricot, Aurelie, Vandekerckhove, Julie, Tamouza, Houda, Zermati, Yael, Ribeil, Jean-Antoine, Djedaini, Kamel, Oruc, Zeliha, Pascal, Virginie, Courtois, Geneviève, Arnulf, Bertrand, Alyanakian, Marie-Alexandra, and Mayeux, Patrick more...
- Subjects
ANEMIA ,ERYTHROPOIETIN ,KIDNEY diseases ,CANCER ,ERYTHROPOIESIS - Abstract
Anemia because of insufficient production of and/or response to erythropoietin (Epo) is a major complication of chronic kidney disease and cancer. The mechanisms modulating the sensitivity of erythroblasts to Epo remain poorly understood. We show that, when cultured with Epo at suboptimal concentrations, the growth and clonogenic potential of erythroblasts was rescued by transferrin receptor 1 (TfR1)-bound polymeric IgA1 (pIgA1). Under homeostatic conditions, erythroblast numbers were increased in mice expressing human IgA1 compared to control mice. Hypoxic stress of these mice led to increased amounts of pIgA1 and erythroblast expansion. Expression of human IgA1 or treatment of wild-type mice with the TfR1 ligands pIgA1 or iron-loaded transferrin (Fe-Tf) accelerated recovery from acute anemia. TfR1 engagement by either pIgA1 or Fe-Tf increased cell sensitivity to Epo by inducing activation of mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) signaling pathways. These cellular responses were mediated through the TfR1-internalization motif, YXX?. Our results show that pIgA1 and TfR1 are positive regulators of erythropoiesis in both physiological and pathological situations. Targeting this pathway may provide alternate approaches to the treatment of ineffective erythropoiesis and anemia. [ABSTRACT FROM AUTHOR] more...
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- 2011
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Catalog
3. Hsp70 regulates erythropoiesis by preventing caspase-3-mediated cleavage of GATA-1.
- Author
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Ribeil, Jean-Antoine, Zermati, Yael, Vandekerckhove, Julie, Cathelin, Severine, Kersual, Joelle, Dussiot, Michaël, Coulon, Séverine, Cruz Moura, Ivan, Zeuner, Ann, Kirkegaard-Sørensen, Thomas, Varet, Bruno, Solary, Eric, Garrido, Carmen, and Hermine, Olivier more...
- Subjects
REGULATION of erythropoiesis ,APOPTOSIS ,TRANSCRIPTION factors ,PROTEOLYSIS ,PEPTIDES - Abstract
Caspase-3 is activated during both terminal differentiation and erythropoietin-starvation-induced apoptosis of human erythroid precursors. The transcription factor GATA-1, which performs an essential function in erythroid differentiation by positively regulating promoters of erythroid and anti-apoptotic genes, is cleaved by caspases in erythroid precursors undergoing cell death upon erythropoietin starvation or engagement of the death receptor Fas. In contrast, by an unknown mechanism, GATA-1 remains uncleaved when these cells undergo terminal differentiation upon stimulation with Epo. Here we show that during differentiation, but not during apoptosis, the chaperone protein Hsp70 protects GATA-1 from caspase-mediated proteolysis. At the onset of caspase activation, Hsp70 co-localizes and interacts with GATA-1 in the nucleus of erythroid precursors undergoing terminal differentiation. In contrast, erythropoietin starvation induces the nuclear export of Hsp70 and the cleavage of GATA-1. In an in vitro assay, Hsp70 protects GATA-1 from caspase-3-mediated proteolysis through its peptide-binding domain. The use of RNA-mediated interference to decrease the Hsp70 content of erythroid precursors cultured in the presence of erythropoietin leads to GATA-1 cleavage, a decrease in haemoglobin content, downregulation of the expression of the anti-apoptotic protein Bcl-X
L , and cell death by apoptosis. These effects are abrogated by the transduction of a caspase-resistant GATA-1 mutant. Thus, in erythroid precursors undergoing terminal differentiation, Hsp70 prevents active caspase-3 from cleaving GATA-1 and inducing apoptosis. [ABSTRACT FROM AUTHOR] more...- Published
- 2007
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4. Real-time RT-PCR detection of CK19, CK7 and MUC1 mRNA for diagnosis of lymph node micrometastases in non small cell lung carcinoma.
- Author
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Saintigny, Pierre, Coulon, Séverine, Kambouchner, Marianne, Ricci, Sylvie, Martinot, Emmanuel, Danel, Claire, Breau, Jean-Luc, and Bernaudin, Jean-François
- Abstract
Metastatic lymph nodes (LNs) are the major prognostic factor in resected non small cell lung carcinoma (NSCLC). However, almost 50% of pN0 patients relapse, suggesting metastatic cells undetected by current staging procedures. A combination of markers [cytokeratins 19 and 7 (CK19, CK7) and mucin type 1 (MUC1) mRNAs] was therefore evaluated by real-time RT-PCR in order to detect occult cancer cells. Forty-three NSCLC tumor samples, 4 micrometastatic, 6 metastatic and 84 histologically negative mediastinal LNs from 19 patients with NSCLC were evaluated as well as blood mononuclear cells from 29 healthy volunteers and 17 benign LNs. When tested on cell lines, RT-PCR was particularly efficient for evaluation of CK19, CK7 and MUC1 mRNA expression. All tumor samples were positive for at least 1 marker and 74% of samples were positive for all 3 markers. CK7 and CK19 mRNA were not detected in benign LN and blood cells from healthy donors in contrast with MUC1 mRNA. Only CK7 and CK19 mRNA were therefore used for evaluation of mediastinal LNs: the 6 histologically metastatic and the 4 micrometastatic LNs were positive for at least one marker. Among the 84 histologically negative LNs, 6 (7%) were positive for at least one marker, potentially changing the stage of 2 out of 19 patients. In conclusion, in our feasibility study, parallel molecular detection of CK19 and CK7 mRNA can be considered a specific diagnostic tool for the assessment of microscopic lymphatic spread. Its prognostic impact remains to be evaluated in a prospective study. © 2005 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR] more...
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- 2005
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5. Neuropilin-1 Expression Characterizes T Follicular Helper (Tfh) Cells Activated during B Cell Differentiation in Human Secondary Lymphoid Organs.
- Author
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Renand, Amédée, Milpied, Pierre, Rossignol, Julien, Bruneau, Julie, Lemonnier, François, Dussiot, Michael, Coulon, Séverine, and Hermine, Olivier
- Subjects
NEUROPILINS ,GENE expression ,T helper cells ,B cell differentiation ,LYMPHOID tissue ,GERMINAL centers ,CELL receptors - Abstract
T follicular helper (Tfh) cells play an essential role in the development of antigen-specific B cell immunity. Tfh cells regulate the differentiation and survival of activated B cells outside and inside germinal centers (GC) of secondary lymphoid organs. They act through cognate contacts with antigen-presenting B cells, but there is no current marker to specifically identify those Tfh cells which productively interact with B cells. Here we show that neuropilin 1 (Nrp1), a cell surface receptor, is selectively expressed by a subset of Tfh cells in human secondary lymphoid organs. Nrp1 expression on Tfh cells correlates with B cell differentiation in vivo and in vitro, is transient, and can be induced upon co-culture with autologous memory B cells in a cell contact-dependent manner. Comparative analysis of ex vivo Nrp1
+ and Nrp1- Tfh cells reveals gene expression modulation during activation. Finally, Nrp1 is expressed by malignant Tfh-like cells in a severe case of angioimmunoblastic T-cell lymphoma (AITL) associated with elevated terminal B cell differentiation. Thus, Nrp1 is a specific marker of Tfh cells cognate activation in humans, which may prove useful as a prognostic factor and a therapeutic target in neoplastic diseases associated with Tfh cells activity. [ABSTRACT FROM AUTHOR] more...- Published
- 2013
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