Coulon S.,University of Paris Descartes |
Dussiot M.,University of Paris Descartes |
Dussiot M.,French Institute of Health and Medical Research |
Dussiot M.,University Paris Diderot |
And 37 more authors.
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, YXXÎ ■. 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. © 2011 Nature America, Inc. All rights reserved. Source
Fremeaux-Bacchi V.,Laboratoire dImmunologie Biologique |
Fremeaux-Bacchi V.,French Institute of Health and Medical Research |
Legendre C.M.,Service de Nephrologie Transplantation |
Legendre C.M.,Paris-Sorbonne University |
Legendre C.M.,French Institute of Health and Medical Research
The role of complement in the biology of kidney transplantation is becoming more and more significant, especially but not only because we now have access to drugs inhibiting complement. After describing the main characteristics of complement biology, both activation of the complement cascade and the many regulatory factors, we will review the precise role of complement in kidney transplant biology. Complement activation has been involved in ischemia-reperfusion injury, in the recurrence of several diseases such as atypical hemolytic uremic syndrome, C3 glomerulopathies, and antiphospholipid syndrome, as well as the process of antibody-mediated rejection, either acute or chronic. There are many potentially interesting drugs interfering with complement inhibition that have been or may be studied in kidney transplantation. Currently, the bulk of data concerns eculizumab, a monoclonal antibody blocking the complement cascade at the C5. Its efficacy has been demonstrated in the treatment and prevention of recurrence of atypical hemolytic uremic syndrome with an overall good safety profile. Although it has been reported to be efficacious to prevent antibody-mediated rejection, properly designed trials are currently being performed to state this efficacy. In addition, randomized trials are, in the process, regarding the prevention of ischemia-reperfusion injury after kidney transplantation. © 2015 International Society of Nephrology. Source
Kerneis S.,University of Paris Descartes |
Kerneis S.,Center dInvestigation Clinique 505 |
Kerneis S.,French Institute of Health and Medical Research |
Kerneis S.,University Pierre and Marie Curie |
And 10 more authors.
Clinical Infectious Diseases
Vaccine-induced antibodies may wane more quickly in persons living with human immunodeficiency virus (HIV) than in healthy individuals. We reviewed the literature on vaccines routinely recommended in HIV-infected patients to estimate how seroprotection decreases over time in those who initially responded to immunization. For each study retrieved from the literature, the decrease of seroprotection was modeled with a log binomial generalized linear model, and data were pooled in a meta-analysis to provide estimates of seroprotection 2 and 5 years after the last vaccine administration. Our analyses confirmed that the duration of seroprotection was shorter in HIV-infected patients and that with current guidelines, a substantial proportion of patients would have lost protective antibodies before a booster was proposed. We therefore discuss the implications for the monitoring of antibody levels and timing of revaccination in these patients. © 2014 The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. Source
Ponsoye M.,University of Paris Descartes |
Frantz C.,University of Paris Descartes |
Ruzejahi N.,University of Paris Descartes |
Nicco C.,University of Paris Descartes |
And 9 more authors.
Annals of the Rheumatic Diseases
Objective Activated T cells are the main component of the inflammatory skin infiltrates that characterise systemic sclerosis (SSc). Our aim was to investigate the efficacy of abatacept, which tempers T-cell activation, in reducing skin fibrosis in complementary mouse models of SSc. Methods The antifibrotic properties of abatacept were evaluated in the mouse models of bleomycin-induced dermal fibrosis and sclerodermatous chronic graft-versushost disease, reflecting early and inflammatory stages of SSc. Thereafter, we studied the efficacy of abatacept in tight skin (Tsk-1) mice, an inflammation-independent mouse model of skin fibrosis. Results Abatacept efficiently prevented bleomycininduced skin fibrosis and was also effective in the treatment of established fibrosis. In this model, abatacept decreased total and activated T-cell, B-cell and monocyte infiltration in the lesional skin. Abatacept did not protect CB17-SCID mice from the development of bleomycin-induced dermal fibrosis, which supports that T cells are necessary to drive the antifibrotic effects of abatacept. Upon bleomycin injections, skin interleukin (IL) 6 and IL-10 levels were significantly reduced upon abatacept treatment. Moreover, treatment with abatacept ameliorated fibrosis in the chronic graft-versushost disease model, but demonstrated no efficacy in Tsk- 1 mice. The tolerance of abatacept was excellent in the three mouse models. Conclusions Using complementary models, we demonstrate that inhibition of T-cell activation by abatacept can prevent and induce the regression of inflammation-driven dermal fibrosis. Translation to human disease is now required, and targeting early and inflammatory stages of SSc sounds the most appropriate for positioning abatacept in SSc. © 2016 BMJ Publishing Group Ltd & European League Against Rheumatism. Source
Auguste T.,French Institute of Health and Medical Research |
Auguste T.,University Paris Est Creteil |
Travert M.,French Institute of Health and Medical Research |
Tarte K.,French Institute of Health and Medical Research |
And 10 more authors.
Angioimmunoblastic T-cell Lymphoma (AITL) is one of the most frequent T-cell lymphoma entities. Follicular helper T lymphocytes (TFH) are recognized as the normal cellular counterpart of the neoplastic component. Despite a clonal T-cell feature and few described recurrent cytogenetic abnormalities, a driving oncogenic event has not been identified so far. It has been recently reported that in mice, heterozygous inactivation of Roquin/Rc3h1, a RING type E3 ubiquitine ligase, recapitulates many of the clinical, histological, and cellular features associated with human AITL. In this study we explored whether ROQUIN alterations could be an initial event in the human AITL oncogenic process. Using microarray and RT-PCR analyses, we investigated the levels of ROQUIN transcripts in TFH tumor cells purified from AITL (n = 8) and reactive tonsils (n = 12) and found similar levels of ROQUIN expression in both. Moreover, we also demonstrated that ROQUIN protein was expressed by AITL TFH (PD1+) cells. We then analysed ROQUIN coding sequence in 12 tumor cell-rich AITL samples and found no mutation in any of the samples. Finally, we analysed the expression of MiR101, a putative partner of ROQUIN involved in the modulation of ICOS expression and found similar levels of expression in tumor and reactive TFH. Altogether, this study shows that neither alteration of ROQUIN gene nor deregulation of miR101 expression is likely to be a frequent recurrent event in AITL. © 2013 Auguste et al. Source