Publications
2013
Lacotte Stéphanie, Decossas Marion, Coz Carole Le, Brun Susana, Muller Sylviane, Dumortier Hélène
Early differentiated CD138(high) MHCII+ IgG+ plasma cells express CXCR3 and localize into inflamed kidneys of lupus mice Article de journal
Dans: PloS One, vol. 8, no. 3, p. e58140, 2013, ISSN: 1932-6203.
Résumé | Liens | BibTeX | Étiquettes: Animals, Autoantibodies, Cell Differentiation, CXCR3, Dumortier, Gene Expression Regulation, Histocompatibility Antigens Class II, I2CT, Immunoglobulin G, Inbred BALB C, Kidney, Leukocyte Common Antigens, Lupus Nephritis, Mice, Plasma Cells, Receptors, Syndecan-1, Team-Dumortier
@article{lacotte_early_2013,
title = {Early differentiated CD138(high) MHCII+ IgG+ plasma cells express CXCR3 and localize into inflamed kidneys of lupus mice},
author = {Stéphanie Lacotte and Marion Decossas and Carole Le Coz and Susana Brun and Sylviane Muller and Hélène Dumortier},
doi = {10.1371/journal.pone.0058140},
issn = {1932-6203},
year = {2013},
date = {2013-01-01},
journal = {PloS One},
volume = {8},
number = {3},
pages = {e58140},
abstract = {Humoral responses are central to the development of chronic autoimmune diseases such as systemic lupus erythematosus. Indeed, autoantibody deposition is responsible for tissue damage, the kidneys being one of the main target organs. As the source of pathogenic antibodies, plasma cells are therefore critical players in this harmful scenario, both at systemic and local levels. The aim of the present study was to analyze plasma cells in NZB/W lupus mice and to get a better understanding of the mechanisms underlying their involvement in the renal inflammation process. Using various techniques (i.e. flow cytometry, quantitative PCR, ELISpot), we identified and extensively characterized three plasma cell intermediates, according to their B220/CD138/MHCII expression levels. Each of these cell subsets displays specific proliferation and antibody secretion capacities. Moreover, we evidenced that the inflammation-related CXCR3 chemokine receptor is uniquely expressed by CD138(high)MHCII(+) plasma cells, which encompass both short- and long-lived cells and mostly produce IgG (auto)antibodies. Expression of CXCR3 allows efficient chemotactic responsiveness of these cells to cognate chemokines, which production is up-regulated in the kidneys of diseased NZB/W mice. Finally, using fluorescence and electron microscopy, we demonstrated the presence of CD138(+)CXCR3(+)IgG(+) cells in inflammatory areas in the kidneys, where they are very likely involved in the injury process. Thus, early differentiated CD138(high)MHCII(+) rather than terminally differentiated CD138(high)MHCII(low) plasma cells may be involved in the renal inflammatory injury in lupus, due to CXCR3 expression and IgG secretion.},
keywords = {Animals, Autoantibodies, Cell Differentiation, CXCR3, Dumortier, Gene Expression Regulation, Histocompatibility Antigens Class II, I2CT, Immunoglobulin G, Inbred BALB C, Kidney, Leukocyte Common Antigens, Lupus Nephritis, Mice, Plasma Cells, Receptors, Syndecan-1, Team-Dumortier},
pubstate = {published},
tppubtype = {article}
}
2010
Lacotte Stéphanie, Dumortier Hélène, Décossas Marion, Briand Jean-Paul, Muller Sylviane
Identification of new pathogenic players in lupus: autoantibody-secreting cells are present in nephritic kidneys of (NZBxNZW)F1 mice Article de journal
Dans: Journal of Immunology (Baltimore, Md.: 1950), vol. 184, no. 7, p. 3937–3945, 2010, ISSN: 1550-6606.
Résumé | Liens | BibTeX | Étiquettes: Animals, Autoantibodies, Autoantigens, B-Lymphocytes, Dumortier, Enzyme-Linked Immunosorbent Assay, Female, Histones, I2CT, Immunoblotting, Immunohistochemistry, Inbred BALB C, Inbred NZB, Lupus Nephritis, Mice, Team-Dumortier
@article{lacotte_identification_2010,
title = {Identification of new pathogenic players in lupus: autoantibody-secreting cells are present in nephritic kidneys of (NZBxNZW)F1 mice},
author = {Stéphanie Lacotte and Hélène Dumortier and Marion Décossas and Jean-Paul Briand and Sylviane Muller},
doi = {10.4049/jimmunol.0902595},
issn = {1550-6606},
year = {2010},
date = {2010-04-01},
journal = {Journal of Immunology (Baltimore, Md.: 1950)},
volume = {184},
number = {7},
pages = {3937--3945},
abstract = {An important hallmark of systemic lupus erythematosus is the production of autoantibodies specific for nuclear Ags, among which nucleosomes and their constituents, DNA and histones. It is widely admitted that some of these autoantibodies contribute largely in lupus pathogenesis because of their nephritogenic potential. However, the underlying mechanisms are still debated. In this study, we analyzed the autoimmune response against histone H2B during the course of the disease in lupus-prone (NZBxNZW)F1 mice, both in lymphoid organs and kidneys, and we assessed its potential involvement in lupus pathogenicity. We found that the N-terminal region of histone H2B represents a preferential target for circulating autoantibodies, which kinetics of appearance positively correlates with disease development. Furthermore, immunization of preautoimmune (NZBxNZW)F1 mice with H2B peptide 1-25 accelerates the disease. Kidney eluates from diseased (NZBxNZW)F1 mice do contain IgG Abs reacting with this peptide, and this H2B sequence was found to be accessible to specific Ab probes in Ag-containing deposits detected in nephritic kidneys. Finally, compared with control normal mice and to young preautoimmune (NZBxNZW)F1 animals, the frequency of cells secreting autoantibodies reacting with peptide 1-25 was significantly raised in the spleen and bone marrow and most importantly on a pathophysiological point of view, locally, in nephritic kidneys of diseased (NZBxNZW)F1 mice. Altogether our results demonstrate the existence in (NZBxNZW)F1 mice of both a systemic and local B cell response targeting the N-terminal region of histone H2B, and highlight the potential implication of this nuclear domain in lupus pathology.},
keywords = {Animals, Autoantibodies, Autoantigens, B-Lymphocytes, Dumortier, Enzyme-Linked Immunosorbent Assay, Female, Histones, I2CT, Immunoblotting, Immunohistochemistry, Inbred BALB C, Inbred NZB, Lupus Nephritis, Mice, Team-Dumortier},
pubstate = {published},
tppubtype = {article}
}
2003
Monneaux Fanny, Lozano José Manuel, Patarroyo Manuel E, Briand Jean-Paul, Muller Sylviane
T cell recognition and therapeutic effect of a phosphorylated synthetic peptide of the 70K snRNP protein administered in MR/lpr mice Article de journal
Dans: European Journal of Immunology, vol. 33, no. 2, p. 287–296, 2003, ISSN: 0014-2980.
Résumé | Liens | BibTeX | Étiquettes: Amino Acid Sequence, Animal, Animals, Autoantibodies, Autoantigens, Autoimmune Diseases, B-Lymphocytes, Cross Reactions, Disease Models, Female, HLA-DR Antigens, HLA-DR Serological Subtypes, HLA-DR1 Antigen, HLA-DR4 Antigen, Humans, I2CT, Immunization, Immunotherapy, Inbred BALB C, Inbred MRL lpr, Lupus Erythematosus, Lupus Nephritis, Mice, Molecular Sequence Data, Monneaux, Peptide Fragments, Phosphorylation, Protein Binding, Ribonucleoprotein, Systemic, T-Lymphocytes, Team-Dumortier, U1 Small Nuclear
@article{monneaux_t_2003,
title = {T cell recognition and therapeutic effect of a phosphorylated synthetic peptide of the 70K snRNP protein administered in MR/lpr mice},
author = {Fanny Monneaux and José Manuel Lozano and Manuel E Patarroyo and Jean-Paul Briand and Sylviane Muller},
doi = {10.1002/immu.200310002},
issn = {0014-2980},
year = {2003},
date = {2003-01-01},
journal = {European Journal of Immunology},
volume = {33},
number = {2},
pages = {287--296},
abstract = {Modifications of self antigens that occur during apoptosis might be involved in the generation of neo-antigens, which can break tolerance and induce autoimmunity. We have previously identified an epitope at residues 131-151 of the U1-70K snRNP protein, recognized by IgG antibodies and CD4+ T cells from at least two strains of lupus mice. With the aim of investigating the possible role of phosphorylation on the antigenicity of peptide 131-151 and to gain a better understanding of how this peptide can drive autoimmune response, we synthesized two peptides phosphorylated on Ser137 and 140, respectively. We show here that peptide P140 phosphorylated on Ser140 is recognized by both CD4+ T cells and antibodies from MRL/lpr mice. Furthermore, intravenous administration to lupus-prone MRL/lpr mice of P140 in saline (but not of the non-phosphorylated peptide) decreased proteinuria and anti-DNA antibody production, and significantly prolonged survival of treated mice. We further demonstrated that P140 is recognized by antibodies from lupus patients and binds to various HLA DR molecules, offering new hope for manipulating T cell response in humans.},
keywords = {Amino Acid Sequence, Animal, Animals, Autoantibodies, Autoantigens, Autoimmune Diseases, B-Lymphocytes, Cross Reactions, Disease Models, Female, HLA-DR Antigens, HLA-DR Serological Subtypes, HLA-DR1 Antigen, HLA-DR4 Antigen, Humans, I2CT, Immunization, Immunotherapy, Inbred BALB C, Inbred MRL lpr, Lupus Erythematosus, Lupus Nephritis, Mice, Molecular Sequence Data, Monneaux, Peptide Fragments, Phosphorylation, Protein Binding, Ribonucleoprotein, Systemic, T-Lymphocytes, Team-Dumortier, U1 Small Nuclear},
pubstate = {published},
tppubtype = {article}
}
2000
Dumortier H, Monneaux F, Jahn-Schmid B, Briand J P, Skriner K, Cohen P L, Smolen J S, Steiner G, Muller S
B and Ŧ cell responses to the spliceosomal heterogeneous nuclear ribonucleoproteins A2 and B1 in normal and lupus mice Article de journal
Dans: Journal of Immunology (Baltimore, Md.: 1950), vol. 165, no. 4, p. 2297–2305, 2000, ISSN: 0022-1767.
Résumé | Liens | BibTeX | Étiquettes: Amino Acid Sequence, Animals, Autoantibodies, B-Lymphocytes, Dumortier, Epitope Mapping, Female, Heterogeneous Nuclear, Heterogeneous-Nuclear Ribonucleoprotein Group A-B, Heterogeneous-Nuclear Ribonucleoproteins, Humans, I2CT, Immunoglobulin G, Inbred BALB C, Inbred C57BL, Inbred CBA, Inbred MRL lpr, Injections, Lupus Nephritis, Lymphocyte Activation, Male, Mice, Molecular Sequence Data, Monneaux, Peptide Fragments, Recombinant Proteins, Ribonucleoproteins, RNA, Spliceosomes, Subcutaneous, T-Lymphocytes, Team-Dumortier, transgenic
@article{dumortier_b_2000,
title = {B and Ŧ cell responses to the spliceosomal heterogeneous nuclear ribonucleoproteins A2 and B1 in normal and lupus mice},
author = {H Dumortier and F Monneaux and B Jahn-Schmid and J P Briand and K Skriner and P L Cohen and J S Smolen and G Steiner and S Muller},
doi = {10.4049/jimmunol.165.4.2297},
issn = {0022-1767},
year = {2000},
date = {2000-08-01},
journal = {Journal of Immunology (Baltimore, Md.: 1950)},
volume = {165},
number = {4},
pages = {2297--2305},
abstract = {Autoantibodies directed against spliceosomal heterogeneous nuclear ribonucleoproteins (hnRNPs) are a typical feature of rheumatoid arthritis, systemic lupus erythematosus, and mixed-connective tissue disease. With the aim of investigating a potential pathogenic role of these Abs, we have studied the Ab response to A2/B1 hnRNPs in different murine models of lupus. The specificity of anti-A2/B1 Abs was tested with a series of 14 overlapping synthetic peptides covering the region 1-206 of A2 that contains most of the epitopes recognized by patients' Abs. A major epitope recognized very early during the course of the disease by Abs from most of MRL lpr/lpr mice but not from other lupus mice and from mice of different MHC haplotypes immunized against B1 was identified in residues 50-70. This peptide contains a highly conserved sequence RGFGFVTF also present in other hnRNPs and small nuclear ribonucleoproteins. Abs reacting with a second A2 epitope identified in residues 35-55 were detectable several weeks later, suggesting an intramolecular B cell epitope spreading during the course of the disease. We identified several T cell epitopes within the region 35-175 that generated an effective Th cell response with IL-2 and IFN-gamma secretion in nonautoimmune CBA/J mice sharing the same MHC haplotype H-2k as MRL/lpr mice. None of the peptides stimulated T cells primed in vivo with B1. Because Abs to peptide 50-70 were detected significantly earlier than Abs reacting with other A2 peptides and the protein itself, it is possible that within the protein, this segment contains residues playing an initiator role in the induction of the anti-A2/B1 and antispliceosome Ab response.},
keywords = {Amino Acid Sequence, Animals, Autoantibodies, B-Lymphocytes, Dumortier, Epitope Mapping, Female, Heterogeneous Nuclear, Heterogeneous-Nuclear Ribonucleoprotein Group A-B, Heterogeneous-Nuclear Ribonucleoproteins, Humans, I2CT, Immunoglobulin G, Inbred BALB C, Inbred C57BL, Inbred CBA, Inbred MRL lpr, Injections, Lupus Nephritis, Lymphocyte Activation, Male, Mice, Molecular Sequence Data, Monneaux, Peptide Fragments, Recombinant Proteins, Ribonucleoproteins, RNA, Spliceosomes, Subcutaneous, T-Lymphocytes, Team-Dumortier, transgenic},
pubstate = {published},
tppubtype = {article}
}