References of "Geenen, Vincent"
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See detailThymus and type 1 diabetes: An update
Geenen, Vincent ULg

in Diabetes Research & Clinical Practice (2012)

Type 1 diabetes (T1D) is a chronic disease resulting from the selective autoimmune destruction of pancreatic islet ß cells. The absence and/or breakdown of immune selftolerance to islet ß cells is now ... [more ▼]

Type 1 diabetes (T1D) is a chronic disease resulting from the selective autoimmune destruction of pancreatic islet ß cells. The absence and/or breakdown of immune selftolerance to islet ß cells is now recognized as the essential cause for the development of the diabetogenic autoimmune response. For a long time, a failure in peripheral tolerogenic mechanisms was regarded as the main source of an inappropriate immune process directed against insulin-secreting ß cells. While defective peripheral self-tolerance still deserves to be further investigated, the demonstration that all members of the insulin gene family are transcribed in thymic epithelial cells (TECs) of different species under the control of the AutoImmune REgulator (AIRE) gene/protein has highlighted the importance of central self-tolerance to insulin-secreting islet b cells. Moreover, there is now evidence that a primary or acquired failure in thymus-dependent central self-tolerance to ß cells plays a primary role in T1D pathogenesis. This novel knowledge is currently translated into the development of innovative tolerogenic/regulatory approaches designed to reprogram the specific immune self-tolerance to islet ß cells. [less ▲]

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See detailAuto-immune gastritis characteristics in a large series of patients with auto-immune thyroiditis.
VALDES SOCIN, Hernan Gonzalo ULg; TOME, M.; LUTTERI, Laurence ULg et al

in XXIVth Belgian Week of Gastroenterology 2012 - Abstract book (2012)

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See detailEditorial
Chentoufi, Aziz Alami; Geenen, Vincent ULg; Giannokakis, Nick et al

in Chentoufi, Aziz Alami; Geenen, Vincent; Giannokakis, Nick (Eds.) et al Type 1 Diabetes Immunological Tolerance and Immunotherapy (2011)

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See detailThyroid and the thymus
Geenen, Vincent ULg

Conference (2011, December 03)

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See detailInvestigations on the mechanisms underlying the thymotropic properties of the growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis.
Goffinet, Lindsay ULg; Bodart, Gwennaëlle ULg; Renard, Chantal et al

Poster (2011, November 18)

Background. The thymus is responsible for thymopoiesis, i.e. the generation of a diverse and self-tolerant T-cell repertoire including self-antigen specific natural regulatory cells. We have shown that ... [more ▼]

Background. The thymus is responsible for thymopoiesis, i.e. the generation of a diverse and self-tolerant T-cell repertoire including self-antigen specific natural regulatory cells. We have shown that two parameters of thymopoiesis, thymic output of new T cells (estimated by sjTREC frequency) and intrathymic proliferation of T-cell precursors (estimated by sj/Dβ TREC ratio) are severely reduced in adult patients with GH deficiency (AGHD) and are restored by GH injections at physiological doses. In patients with AGHD, there is a very positive correlation between sjTREC frequency and plasma concentrations of IGF-1, the principal mediator of GH action (1). Treatment of HIV+ patients with high pharmacological doses of GH is associated with increased thymic mass and output of circulating naïve and total CD4+ T cells (2). In addition, previous studies have suggested thymic epithelial cells (TEC) and/or thymocytes (thymic T cells) could transcribe the GH gene (3). Objectives and hypothesis. These studies analysed the question of GH transcription and regulation in primary cultures of human (h) TEC. We also investigated the hypothesis that the thymotropic properties of the somatotrope GH/IGF-1 axis could be mediated by thymic interleukin 7 (IL-7), which plays a crucial role in promoting V(D)J recombination at the TCR locus. Results. Primary hTEC cultures were treated with natural secretagogues of pituitary GH, GH releasing hormone (GHRH) and ghrelin. Using sensitive RT-qPCR, we detected neither any transcript of GH or GHV (placental GH variant) in cultured hTEC, nor any transcript of PIT1, the specific transcription factor of pituitary GH. Similarly, the protein GH was detected neither in the cytoplasm nor in the supernatant of cultured hTEC. Only at 1 nM, GH treatment enhanced IGF1 transcription by cultured hTEC. Of high interest, treatment with GH, ghrelin and IGF-1 promoted IL7 transcription by cultured hTEC, but only IGF-1 and epidermal growth factor (EGF) markedly stimulated IL-7 secretion by hTEC in a dose- and time-dependent manner. The specificity of IGF-1 action was demonstrated by its inhibition after treatment with αIR3, a monoclonal antibody against the type 1 IGF receptor. Conclusions and perspectives. Since primary cultures of hTEC neither transcribe nor secrete any significant amount of GH, the thymotropic effects of the GH/IGF-1 axis seem to depend only on systemic endocrine GH. Local thymic IGF-1 could partially mediate GH action within the thymus and act upon thymopoiesis in parallel with systemic IGF-1. Most importantly, thymic IL-7 appears to be an important mediator of the thymotropic properties of the GH/IGF-1 axis. Further knowledge in this domain will be gained with the use and supplementation of Ghrh-/- mice that will be soon available in our laboratory. References 1. Morrhaye G. et al., PLoS ONE 2009, 4:e5668. 2. Napolitano LA et al. J Clin Invest 2008, 118:1085. 3. Smaniotto S et al., Endocrinology 2005, 146:3005. 4. Taub DD, Murphy WJ and Longo DL. Curr Opin Pharmacol 2010, 10:408. (Supported by F.R.S.-FNRS and a Pfizer Independent Research Grant.) [less ▲]

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See detailMechanisms of the anti-obesity effects of oxytocin in diet-induced obese rats
Deblon, Nicolas; Veyrat-Durebex, Christelle; Bourgoin, Lucie et al

in PLoS ONE (2011), 6

Apart from its role during labor and lactation, oxytocin is involved in several other functions. Interestingly, oxytocin- and oxytocin receptor-deficient mice develop late-onset obesity with normal food ... [more ▼]

Apart from its role during labor and lactation, oxytocin is involved in several other functions. Interestingly, oxytocin- and oxytocin receptor-deficient mice develop late-onset obesity with normal food intake, suggesting that the hormone might exert a series of beneficial metabolic effects. This was recently confirmed by data showing that central oxytocin infusion causes weight loss in diet-induced obese mice. The aim of the present study was to unravel the mechanisms underlying such beneficial effects of oxytocin. Chronic central oxytocin infusion was carried out in high fat diet-induced obese rats. Its impact on body weight, lipid metabolism and insulin sensitivity was determined. We observed a dose-dependent decrease in body weight gain, increased adipose tissue lipolysis and fatty acid β-oxidation, as well as reduced glucose intolerance and insulin resistance. The additional observation that plasma oxytocin levels increased upon central infusion suggested that the hormone might affect adipose tissue metabolism by direct action. This was demonstrated using in vitro, ex vivo, as well as in vivo experiments. With regard to its mechanism of action in adipose tissue, oxytocin increased the expression of stearoyl-coenzyme A desaturase 1, as well as the tissue content of the phospholipid precursor, N-oleoyl-phosphatidylethanolamine , the biosynthetic precursor of the oleic acid-derived PPAR-alpha activator, oleoylethanolamide. Because PPAR-alpha regulates fatty acid β-oxidation, we hypothesized that this transcription factor might mediate the oxytocin effects. This was substantiated by the observation that, in contrast to its effects in wild-type mice, oxytocin infusion failed to induce weight loss and fat oxidation in PPAR-alpha-deficient animals. Altogether, these results suggest that oxytocin administration could represent a promising therapeutic approach for the treatment of human obesity and type 2 diabetes. [less ▲]

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See detailEmbryologie générale et moléculaire
Geenen, Vincent ULg

Learning material (2011)

Notes du cours d'Embryologie - M1BOE

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See detailRheumatoid arthritis and pregnancy: evolution of disease activity and pathophysiological considerations for drug use
Hazes, Johanna M.W.; Coulie, Pierre G.; Geenen, Vincent ULg et al

in Rheumatology (2011)

It has long been known that pregnancy and childbirth have a profound effect on the disease activity of rheumatic diseases. For clinicians, the management of patients with RA wishing to become pregnant ... [more ▼]

It has long been known that pregnancy and childbirth have a profound effect on the disease activity of rheumatic diseases. For clinicians, the management of patients with RA wishing to become pregnant involves the challenge of keeping disease activity under control and adequately adapting drug therapy during pregnancy and post-partum. This article aims to summarize the current evidence on the evolution of RA disease activity during and after pregnancy and the use of anti-rheumatic drugs around this period. Of recent interest is the potential use of anti-TNF compounds in the preconception period and during pregnancy. Accumulating experience with anti-TNF therapy in other immune-mediated inflammatory diseases, such as Crohn’s disease, provides useful insights for the use of TNF blockade in pregnant women with RA, or RA patients wishing to become pregnant. [less ▲]

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See detailType 1 diabetes immunological tolerance and immunotherapy
ALAMI CHENTOUFI, Aziz; GIANNOUKAKIS, Nick; Geenen, Vincent ULg

Book published by Hindawi (2011)

Type 1 diabetes (T1D) is a chronic autoimmune disorder associated, in genetically susceptible individuals, with the generation and activation of autoreactive CD4+ and CD8+ T cells that infiltrate the ... [more ▼]

Type 1 diabetes (T1D) is a chronic autoimmune disorder associated, in genetically susceptible individuals, with the generation and activation of autoreactive CD4+ and CD8+ T cells that infiltrate the pancreas and selectively destroy the insulin-producing β-cells in the islets. The impairment of T-cell tolerance in T1D has been reported at many levels including abnormal self-antigen presentation in the thymus and periphery, autoreactive T-cell resistance to apoptosis, unbalanced immunoregulatory T-cell function, and deregulation of Th1/Th2/Th17 axes. Despite the identification of type1 diabetes-associated autoantigens and their derived CD4+ and CD8+ T-cell epitopes, numerous antigen-specific immunoregulatory therapies have failed when evaluated for their utility in the prevention and treatment of T1D. In this special issue, we invite authors to submit original research and review articles highlighting the recent advances that have broadened our understanding of immunological tolerance and T1D vaccine strategies. Also, we welcome papers that seek to define immunoregulatory properties of T cells to provide new insights as to their potential for clinical use. We are interested in articles that explore salient aspects of T1D-associated tolerance and immunotherapy. Potential topics include, but are not limited to: * T1D-associated central and peripheral tolerance mechanisms * Elucidating the functional impairment in immunoregulatory T-cell function in T1D * New animal models to test and understand dysfunctional immunity in T1D * Identification of new beta islet-specific autoantigens * Development of antigen-based immunotherapeutic strategies to prevent or treat T1D * Clinical trials with novel antigen-specific immunoregulatory therapies [less ▲]

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See detailThymic self-antigen expression for the design of a negative/tolerogenic self-vaccine against type 1 diabetes
Alami Chentoufi; Geenen, Vincent ULg

in Clinical & Developmental Immunology (2011)

Before being able to react against infectious non-self antigens, the immune system has to be educated in the recognition and tolerance of neuroendocrine proteins and this critical process takes place only ... [more ▼]

Before being able to react against infectious non-self antigens, the immune system has to be educated in the recognition and tolerance of neuroendocrine proteins and this critical process takes place only in the thymus. The development of the autoimmune diabetogenic response results from a thymus dysfunction in programming central self-tolerance to pancreatic insulin-secreting islet β cells, leading to the breakdown of immune homeostasis with an enrichment of islet β-cell reactive effector T cells and a deficiency of β-cell specific natural regulatory T cells (nTregs) in the peripheral T-lymphocyte repertoire. Insulin-like growth factor 2 (IGF-2) is the dominant member of the insulin family expressed during fetal life by the thymic epithelium under the control of the autoimmune regulator (AIRE) gene/protein. Based on the close homology and cross-tolerance between insulin, the primary T1D autoantigen, and IGF-2, the dominant self-antigen of the insulin family, a novel type of vaccination, so-called “negative/tolerogenic self-vaccination”, is currently being developed for prevention and cure of T1D. If this approach were found to be effective for reprogramming immunological tolerance in T1D, it could pave the way for the design of other self-vaccines against autoimmune endocrine diseases, as well as other organ-specific autoimmune diseases. [less ▲]

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See detailPreliminary characterisation of a transgenic mouse with selective Igf2 depletion in the thymic epithelium
Mottet, Marie ULg; Martens, Henri ULg; Renard-Charlet, Chantal et al

in Scandinavian Journal of Immunology (2011, April)

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See detailInsulin-like growth factor 1 (IGF-1) promotes interleukin 7 (IL-7) synthesis and secretion by primary cultures of human thymic epithelial cells
Goffinet, Lindsay ULg; Renard-Charlet, Chantal; Martens, Henri ULg et al

in Scandinavian Journal of Immunology (2011, April), 73

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See detailL'infusion chronique et centrale d'ocytocine améliore la résistance à l'insuline induite par une nourriture riche en lipides chez le rat
Deblon, Nicolas; Veyrat-Durebex, Christelle; Legros, Jean-Jacques ULg et al

Conference (2011, March 23)

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