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Institution

French Institute of Health and Medical Research

GovernmentParis, France
About: French Institute of Health and Medical Research is a government organization based out in Paris, France. It is known for research contribution in the topics: Population & Receptor. The organization has 109367 authors who have published 174236 publications receiving 8365503 citations.


Papers
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Journal ArticleDOI
TL;DR: Important biological and pharmacological disparities in pre-clinical research and human translational studies are highlighted, and analyses of clinical trial failures and recent successes provide a rational pathway to MSC regulatory approval and deployment for disorders with unmet medical needs.

1,009 citations

Journal ArticleDOI
TL;DR: These findings support the efficacy and safety of the use of bilateral stimulation of the internal globus pallidus in selected patients with primary generalized dystonia.
Abstract: BACKGROUND: Severe forms of dystonia respond poorly to medical treatment. Deep-brain stimulation is a reversible neurosurgical procedure that has been used for the treatment of dystonia, but assessment of its efficacy has been limited to open studies. METHODS: We performed a prospective, controlled, multicenter study assessing the efficacy and safety of bilateral pallidal stimulation in 22 patients with primary generalized dystonia. The severity of dystonia was evaluated before surgery and 3, 6, and 12 months postoperatively during neurostimulation, with the use of the movement and disability subscores of the Burke-Fahn-Marsden Dystonia Scale (range, 0 to 120 and 0 to 30, respectively, with higher scores indicating greater impairment). Movement scores were assessed by a review of videotaped sessions performed by an observer who was unaware of treatment status. At three months, patients underwent a double-blind evaluation in the presence and absence of neurostimulation. We also assessed the patients' quality of life, cognition, and mood at baseline and 12 months. RESULTS: The dystonia movement score improved from a mean (+/-SD) of 46.3+/-21.3 before surgery to 21.0+/-14.1 at 12 months (P<0.001). The disability score improved from 11.6+/-5.5 before surgery to 6.5+/-4.9 at 12 months (P<0.001). General health and physical functioning were significantly improved at month 12; there were no significant changes in measures of mood and cognition. At the three-month evaluation, dystonia movement scores were significantly better with neurostimulation than without neurostimulation (24.6+/-17.7 vs. 34.6+/-12.3, P<0.001). There were five adverse events (in three patients); all resolved without permanent sequelae. CONCLUSIONS: These findings support the efficacy and safety of the use of bilateral stimulation of the internal globus pallidus in selected patients with primary generalized dystonia.

1,008 citations

Journal ArticleDOI
TL;DR: The results expand the potential pathogenic roles of aberrant lupus neutrophils and suggest that dysregulation of NET formation and its subsequent responses may play a prominent deleterious role.
Abstract: An abnormal neutrophil subset has been identified in the PBMC fractions from lupus patients. We have proposed that these low-density granulocytes (LDGs) play an important role in lupus pathogenesis by damaging endothelial cells and synthesizing increased levels of proinflammatory cytokines and type I IFNs. To directly establish LDGs as a distinct neutrophil subset, their gene array profiles were compared with those of autologous normal-density neutrophils and control neutrophils. LDGs significantly overexpress mRNA of various immunostimulatory bactericidal proteins and alarmins, relative to lupus and control neutrophils. In contrast, gene profiles of lupus normal-density neutrophils do not differ from those of controls. LDGs have heightened capacity to synthesize neutrophils extracellular traps (NETs), which display increased externalization of bactericidal, immunostimulatory proteins, and autoantigens, including LL-37, IL-17, and dsDNA. Through NETosis, LDGs have increased capacity to kill endothelial cells and to stimulate IFN-α synthesis by plasmacytoid dendritic cells. Affected skin and kidneys from lupus patients are infiltrated by netting neutrophils, which expose LL-37 and dsDNA. Tissue NETosis is associated with increased anti-dsDNA in sera. These results expand the potential pathogenic roles of aberrant lupus neutrophils and suggest that dysregulation of NET formation and its subsequent responses may play a prominent deleterious role.

1,007 citations

Journal ArticleDOI
TL;DR: DC-derived exosomes accumulate a defined subset of cellular proteins reflecting their endosomal biogenesis and accounting for their biological function, and exosome production is downregulated upon DC maturation, indicating that in vivo,Exosomes are produced by immature DCs in peripheral tissues.
Abstract: Exosomes are membrane vesicles secreted by hematopoietic cells upon fusion of late multivesicular endosomes with the plasma membrane. Dendritic cell (DC)-derived exosomes induce potent antitumor immune responses in mice, resulting in the regression of established tumors (Zitvogel, L., A. Regnault, A. Lozier, J. Wolfers, C. Flament, D. Tenza, P. Ricciardi-Castagnoli, G. Raposo, and S. Amigorena. 1998. Nat. Med. 4:594–600). To unravel the molecular basis of exosome-induced immune stimulation, we now analyze the regulation of their production during DC maturation and characterize extensively their protein composition by peptide mass mapping. Exosomes contain several cytosolic proteins (including annexin II, heat shock cognate protein hsc73, and heteromeric G protein Gi2α), as well as different integral or peripherally associated membrane proteins (major histocompatiblity complex class II, Mac-1 integrin, CD9, milk fat globule-EGF-factor VIII [MFG-E8]). MFG-E8, the major exosomal component, binds integrins expressed by DCs and macrophages, suggesting that it may be involved in exosome targeting to these professional antigen-presenting cells. Another exosome component is hsc73, a cytosolic heat shock protein (hsp) also present in DC endocytic compartments. hsc73 was shown to induce antitumor immune responses in vivo, and therefore could be involved in the exosome's potent antitumor effects. Finally, exosome production is downregulated upon DC maturation, indicating that in vivo, exosomes are produced by immature DCs in peripheral tissues. Thus, DC-derived exosomes accumulate a defined subset of cellular proteins reflecting their endosomal biogenesis and accounting for their biological function.

1,006 citations

Journal ArticleDOI
TL;DR: It is reported that the nonclassic human leukocyte antigen (HLA) class I molecule HLA‐G is responsible for the immunomodulatory properties of MSCs and it is demonstrated that in addition to their action on the adaptive immune system, M SCs, through HLA•G5, affect innate immunity by inhibiting both NK cell‐mediated cytolysis and interferon‐γ secretion.
Abstract: Adult bone marrow-derived mesenchymal stem cells (MSCs) are multipotent cells that are the subject of intense investigation in regenerative medicine. In addition, MSCs possess immunomodulatory properties with therapeutic potential to prevent graft-versus-host disease (GvHD) in allogeneic hematopoietic cell transplantation. Indeed, MSCs can inhibit natural killer (NK) function, modulate dendritic cell maturation, and suppress allogeneic T-cell response. Here, we report that the nonclassic human leukocyte antigen (HLA) class I molecule HLA-G is responsible for the immunomodulatory properties of MSCs. Our data show that MSCs secrete the soluble isoform HLA-G5 and that such secretion is interleukin-10-dependent. Moreover, cell contact between MSCs and allostimulated T cells is required to obtain a full HLA-G5 secretion and, as consequence, a full immunomodulation from MSCs. Blocking experiments using neutralizing anti-HLA-G antibody demonstrate that HLA-G5 contributes first to the suppression of allogeneic T-cell proliferation and then to the expansion of CD4(+)CD25(high)FOXP3(+) regulatory T cells. Furthermore, we demonstrate that in addition to their action on the adaptive immune system, MSCs, through HLA-G5, affect innate immunity by inhibiting both NK cell-mediated cytolysis and interferon-gamma secretion. Our results provide evidence that HLA-G5 secreted by MSCs is critical to the suppressive functions of MSCs and should contribute to improving clinical therapeutic trials that use MSCs to prevent GvHD.

1,002 citations


Authors

Showing all 109539 results

NameH-indexPapersCitations
Guido Kroemer2361404246571
Pierre Chambon211884161565
Peer Bork206697245427
Ronald M. Evans199708166722
Raymond J. Dolan196919138540
Matthew Meyerson194553243726
Charles A. Dinarello1901058139668
Julie E. Buring186950132967
Tadamitsu Kishimoto1811067130860
Didier Raoult1733267153016
Giuseppe Remuzzi1721226160440
Zena Werb168473122629
Nahum Sonenberg167647104053
Philippe Froguel166820118816
Gordon J. Freeman164579105193
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
202368
2022306
20217,549
20207,367
20196,969
20186,607