References of "Geenen, Vincent"
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See detailHistoire du thymus : d'un organe vestigial à la programmation de la tolérance immunitaire
Geenen, Vincent ULg

in Medecine Sciences : M/S (2017), 33(6-7), 634-644

This synthesis presents the most important disruptions of conceptions about the thymus since its discovery in Antique Greece. For centuries, the thymus has been considered as a vestigial organ, and its ... [more ▼]

This synthesis presents the most important disruptions of conceptions about the thymus since its discovery in Antique Greece. For centuries, the thymus has been considered as a vestigial organ, and its role in T-lymphocyte differentiation has been proposed only in the 1960’s. Most recent studies attribute to the thymus an essential and unique role in the programming of central immunological self-tolerance. The basal mechanism implicated in this function is the transcription in thymic epithelium of genes encoding precursors of self-antigens. Processing of these latters leads to presentation of self-antigens by the major histocompatibility complex (MHC) machinery expressed by thymic epithelial and dendritic cells. During fetal life, this presentation drives negative selection of T-cell clones harboring receptors with high affinity for these complexes MHC/self-antigen. After birth, this presentation promotes the generation of regulatory T cells specific for these complexes. A number of studies, as well as the identification of Aire and Fezf2 genes, have shown that a thymus dysfunction plays a crucial role in the development of organ-specific autoimmunity. [less ▲]

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See detailWorld Thyroid Day 2017 - Press annoucement
Moreno-Reyes, Rodrigo; Bex, Marie; Corvilain, Bernard et al

Article for general public (2017)

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See detailA surprising and dramatic neuroendocrine-immune phenotype of mice deficient in Growth Hormone-Releasing Hormone (GHRH)
Farhat, Khalil; Bodart, Gwennaëlle ULg; RENARD, Jeanne de Chantal ULg et al

Poster (2017, May 23)

In the framework of close interactions between the immune and neuroendocrine systems, Growth Hormone (GH) has been proposed to exert significant effects on the immune system, but there is not yet a ... [more ▼]

In the framework of close interactions between the immune and neuroendocrine systems, Growth Hormone (GH) has been proposed to exert significant effects on the immune system, but there is not yet a consensus about GH immunomodulatory properties. These studies investigated the immune and anti-infectious response of dwarf Ghrh-/- mice presenting a severe deficiency of the GHRH/GH/IGF-1 axis. In basal conditions, thymic parameters and T-cell responses of Ghrh-/- mice were not severely affected but a constant B-cell lymphopaenia was observed. Thus, we investigated vaccine and anti-infectious responses of Ghrh-/- mice toward Streptococcus pneumonia, a B-dependent pathogen, Ghrh-/- mice were unable to trigger production of specific IgM and IgG against serotype 1 pneumococcal polysaccharide (PPS) after vaccination with either native PPS (Pnx23) or protein-PPS conjugate (Prev-13) vaccines. These vaccines both include the serotype 1 (our S.pneumoniae strain) and provide an effective protection in mice. A short GH supplementation to Ghrh-/- mice (1 daily injection of 1 mg/kg GH for 4 weeks) restored IgM and IgG response to Pnx23 vaccine but not to Prev-13. This suggests that GH could exert distinct impacts upon spenic areas. Furthermore, after intranasal instillation of a non-lethal dose (defined by the full clearance by WT C57BL/6 mice after 24h) of serotype 1 S.pneumoniae, Ghrh-/- mice exhibited a dramatic susceptibility. This was proved by a marked time-dependent increase in pulmonary bacterial, a septicemia already 24h after infection and a survival limit of 72h. We also observed a dramatic decrease in lung B- and T-cell populations and an increase in proportion of inflammatory macrophages. By contrast, wild-type and heterozygote mice completely cleared S.pneumoniae infection after 24h. In conclusion, our data show without ambiguity that the somatotrope GHRH/GH/IGF-1 axis plays an important and unsuspected role in defense against S.Pneumoniae. [less ▲]

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See detailA surprising and dramatic neuroendocrine-immune phenotype of mice deficient in Growth Hormone-Releasing Hormone (GHRH)
Farhat, Khalil ULg; Bodart, Gwennaëlle ULg; Renard, chantal et al

Poster (2017, May)

In the framework of close interactions between the immune and neuroendocrine systems, Growth Hormone (GH) has been proposed to exert significant effects on the immune system, but there is not yet a ... [more ▼]

In the framework of close interactions between the immune and neuroendocrine systems, Growth Hormone (GH) has been proposed to exert significant effects on the immune system, but there is not yet a consensus about GH immunomodulatory properties. These studies investigated the immune and anti-infectious response of dwarf Ghrh-/- mice presenting a severe deficiency of the GHRH/GH/IGF-1 axis. In basal conditions, thymic parameters and T-cell responses of Ghrh-/- mice were not severely affected but a constant B-cell lymphopaenia was observed. Thus, we investigated vaccine and anti-infectious responses of Ghrh-/- mice toward Streptococcus pneumonia, a B-dependent pathogen, Ghrh-/- mice were unable to trigger production of specific IgM and IgG against serotype 1 pneumococcal polysaccharide (PPS) after vaccination with either native PPS (Pnx23) or protein-PPS conjugate (Prev-13) vaccines. These vaccines both include the serotype 1 (our S.pneumoniae strain) and provide an effective protection in mice. A short GH supplementation to Ghrh-/- mice (1 daily injection of 1 mg/kg GH for 4 weeks) restored IgM and IgG response to Pnx23 vaccine but not to Prev-13. This suggests that GH could exert distinct impacts upon spenic areas. Furthermore, after intranasal instillation of a non-lethal dose (defined by the full clearance by WT C57BL/6 mice after 24h) of serotype 1 S.pneumoniae, Ghrh-/- mice exhibited a dramatic susceptibility. This was proved by a marked time-dependent increase in pulmonary bacterial, a septicemia already 24h after infection and a survival limit of 72h. We also observed a dramatic decrease in lung B- and T-cell populations and an increase in proportion of inflammatory macrophages. By contrast, wild-type and heterozygote mice completely cleared S.pneumoniae infection after 24h. In conclusion, our data show without ambiguity that the somatotrope GHRH/GH/IGF-1 axis plays an important and unsuspected role in defense against S.Pneumoniae. [less ▲]

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See detailLe boom des maladies auto-immunes.
Luong, Julie; GEENEN, Vincent ULg

Article for general public (2017)

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See detailMechanisms of Igf2 inhibition in thymic epithelial cells infected with CVB4 E2
Michaux, Hélène ULg; Charlet-Renard, Chantal; Martens, Henri ULg et al

Poster (2017, March 12)

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See detailL'ocytocine et la biologie du coup de foudre
Geenen, Vincent ULg

Conference given outside the academic context (2017)

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See detailVoyage[s] à travers le thymus
Geenen, Vincent ULg

in Science et Culture (2017), (465), 14-15

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See detailThe somatotrope Growth Hormone-Releasing Hormone/Growth Hormone/Insulin-like Growth Factor 1 axis in immunoregulation and immunosenescence
Bodart, Gwennaëlle ULg; Farhat, Khalil; RENARD, Jeanne de Chantal ULg et al

in Savino, Wilson; Guaraldi, Federica (Eds.) Endocrine Immunology (2017)

Most scientific reports debate the thymotropic and immuno-stimulating properties of the somato- trope growth hormone-releasing hormone (GHRH)/growth hormone (GH)/insulin-like growth factor (IGF)-1 axis ... [more ▼]

Most scientific reports debate the thymotropic and immuno-stimulating properties of the somato- trope growth hormone-releasing hormone (GHRH)/growth hormone (GH)/insulin-like growth factor (IGF)-1 axis, but there is still some disagreement about the physiological role of this axis in basal conditions. Moreover, some authors have hypothesized that the physiological role of the somato- trope axis only appears in stressful conditions (such as sepsis or infective and inflammatory diseases). This chapter will provide an extended overview of the expression of the components (signals and receptors) of the somatotrope axis and their properties on cells of the innate and adaptive immune system. It will also summarize some clinical studies suggesting a benefit for a short-term GH treat- ment in acute immunodeficiencies, and the importance of GH supplementation in adult GH defi- ciency. A new transgenic mouse model, the hypothalamic GHRH-deficient (Ghrh–/–) mouse, which exhibits a severe deficiency of the somatotrope axis, will be presented since it will be of great help in further deciphering the regulation by the GHRH/GH/IGF-1 axis on both immune development and function. Finally, we will discuss the implication of aging-related somatopause in relation to the general context of Immunosenescence. [less ▲]

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See detailL'Homme peut-il devenir immortel ?
Geenen, Vincent ULg

Conference given outside the academic context (2017)

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See detailLes écoles liégeoises de physiologie et de médecine aux 19e et 20e siècle
Geenen, Vincent ULg

Conference given outside the academic context (2017)

La physiologie constitue une véritable révolution à l’époque de Claude Bernard (1813-1878) qui l’institue alors comme le véritable socle de la médecine expérimentale moderne. Avec Charles Darwin, il est ... [more ▼]

La physiologie constitue une véritable révolution à l’époque de Claude Bernard (1813-1878) qui l’institue alors comme le véritable socle de la médecine expérimentale moderne. Avec Charles Darwin, il est un des géants de la science du XIXe siècle et ces deux grands auteurs vont exercer une profonde influence sur de nombreux disciples à l’Université de Liège. Dans le même temps, Liège héberge aussi l’Allemand Théodore Schwann, auteur de la théorie cellulaire selon laquelle la cellule est l’unité de base des mondes animal et végétal. Grâce aux travaux de Edouard Van Beneden, Léon Fredericq et Marcel Florkin, l’Université de Liège acquiert une réputation mondiale. Il est important de rappeler que de véritables révolutions scientifiques ont eu lieu dans le passé, alors que la révolution génétique se déroule sous nos yeux. Les changements que cette dernière produit sont si profonds et si prometteurs que nous pourrions être tentés de négliger notre héritage en le considérant comme dépassé ou inintéressant. Le rappel de l’œuvre gigantesque des physiologistes de l’Université de Liège démontre néanmoins l’inconscience d’un tel oubli. La physiologie contemporaine a de plus en plus déserté les domaines de l’intégration pour se concentrer vers des démarches de plus en plus réductionnistes. Nous pensons toutefois que les voies de l’intégration ne sont pas complètement interdites et qu’il existe encore de nombreux chemins à explorer, ne serait-ce que celui par lequel les systèmes nerveux et endocrine interviennent dans le contrôle de nos défenses immunitaires vis-à-vis des agressions extérieures et, inversement, comment le système immunitaire est capable d’influencer les systèmes nerveux et endocrine. [less ▲]

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See detailA surprising and dramatic neuroendocrine-immune phenotype of mice deficient in Growth Hormone-Releasing Hormone (GHRH)
Farhat, Khalil; Bodart, Gwennaelle; Martens, Henri ULg et al

in Neuroimmunomodulation (2017)

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See detailThe use of oxytocin to improve feeding and social skills in infants with Prader-Willi syndrome
Tauber, Maïthé; Boulanouar, Kader; Gwenaelle, Diene et al

in Pediatrics (2017), 139(2),

BACKGROUND AND OBJECTIVES: Patients with Prader–Willi syndrome (PWS) display poor feeding and social skills as infants and fewer hypothalamic oxytocin (OXT)-producing neurons were documented in adults ... [more ▼]

BACKGROUND AND OBJECTIVES: Patients with Prader–Willi syndrome (PWS) display poor feeding and social skills as infants and fewer hypothalamic oxytocin (OXT)-producing neurons were documented in adults. Animal data demonstrated that early treatment with OXT restores sucking after birth. Our aim is to reproduce these data in infants with PWS. METHODS: We conducted a phase 2 escalating dose study of a short course (7 days) of intranasal OXT administration. We enrolled 18 infants with PWS under 6 months old (6 infants in each step) who received 4 IU of OXT either every other day, daily, or twice daily. We investigated the tolerance and the effects on feeding and social skills and changes in circulating ghrelin and brain connectivity by functional MRI. RESULTS: No adverse events were reported. No dose effect was observed. Sucking assessed by the Neonatal Oral-Motor Scale was abnormal in all infants at baseline and normalized in 88% after treatment. The scores of Neonatal Oral-Motor Scale and videofluoroscopy of swallowing significantly decreased from 16 to 9 (P < .001) and from 18 to 12.5 (P < .001), respectively. Significant improvements in Clinical Global Impression scale scores, social withdrawal behavior, and mother–infant interactions were observed. We documented a significant increase in acylated ghrelin and connectivity of the right superior orbitofrontal network that correlated with changes in sucking and behavior. CONCLUSIONS: OXT is well tolerated in infants with PWS and improves feeding and social skills. These results open perspectives for early treatment in neurodevelopment diseases with feeding problems. [less ▲]

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See detailSevere deficiency of the somatotrope GHRH/GH/IGF-1 axis induces a dramatic susceptibility to Streptococcus pneumoniae infection.
Farhat, Khalil ULg; Bodart, Gwennaëlle ULg; Desmet, Christophe ULg et al

Poster (2016, November 07)

Deletion of the growth hormone-releasing hormone gene (Ghrh) results in a severe deficiency of the somatotrope GHRH-GH-IGF-1 axis causing dwarf phenotype that can be reversed by GH or GHRH supplementation ... [more ▼]

Deletion of the growth hormone-releasing hormone gene (Ghrh) results in a severe deficiency of the somatotrope GHRH-GH-IGF-1 axis causing dwarf phenotype that can be reversed by GH or GHRH supplementation (Alba & Salvatori, Endocrinology 2004;145:4134). In basal conditions, the immunological phenotype of Ghrh-/- mice is not markedly disturbed except for a decrease in B cells and an increase in generation of thymic (t) Treg cells (submitted for publication). These data prompted us to investigate immune responses of Ghrh-/- mice using vaccination and infection by S. pneumoniae as models since the response to both stimuli rely on the innate immune system and B cells. Ghrh-/- mice were unable to trigger production of specific IgM and IgG against serotype 1 pneumococcal polysaccharide (PPS) after vaccination with either native PPS (Pnx23) or protein-PPS conjugate (Prev-13) vaccines. A short GH supplementation to Ghrh-/- mice (1 daily injection of 1 mg/kg GH for 4 weeks) restored IgM and IgG response to Pnx23 vaccine but not to Prev-13. This suggests that GH differently impacts on B-1, marginal zone B-2 or innate B-1 B cells. Furthermore, after intranasal instillation of a non-lethal dose of serotype 1 S. pneumoniae, Ghrh-/- mice exhibited a dramatic susceptibility reflected by bacteremia 24h after infection and a survival limit of 72 h, compared to WT C57BL/6 mice that need only 24h to clear infection. The possible impact of GH deficiency on components of the innate immune system that play an important role in defense of the respiratory tract against pneumococcal infection is under current investigation. (*Equal first and last authors. KF is supported by a research grant from the Lebanese Government; GB is Research Assistant, CD is Research Associate, and VG is Research Director at the NFSR of Belgium). [less ▲]

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See detailIn-utero coxsackievirus B4 infection of the mouse thymus
Jaïdane, Hela; Halouani, Aymen; Jmii, H. et al

in Clinical & Experimental Immunology (2016), Sous presse

Type B coxsackievirus (CV-B) infections are involved frequently in the triggering of several autoimmune diseases such as myocarditis, dilated cardiomyopathy, pericarditis, pancreatitis, type 1 diabetes ... [more ▼]

Type B coxsackievirus (CV-B) infections are involved frequently in the triggering of several autoimmune diseases such as myocarditis, dilated cardiomyopathy, pericarditis, pancreatitis, type 1 diabetes, encephalitis, thyroiditis or Sjo€gren’s syndrome. Serological and virological evidence suggests that maternal infections during pregnancy can play a role in the appearance of these diseases in offspring. The current study aims to explore the effect of an in-utero CV-B infection on the fetal thymus, the central site for programming immunological self-tolerance. In this perspective, female Swiss albino mice were inoculated intraperitoneally or orally with the diabetogenic CV-B4 E2 strain at gestational days 10 or 17. Offspring were killed at different post-inoculation times, and their thymuses were analysed for evidence of infection and alterations in thymic T cell subsets. In-utero CV-B infection of the thymus was demonstrated during the course of vertical transmission, as attested by viral RNA and infectious virus detection in most analysed samples. No histopathological changes were evident. Thymic T cells were not depleted, despite being positive for viral RNA. As evidenced by flow cytometry analysis, CV-B infection of the fetal thymus induced significant changes of thymic T cell populations, particularly with maternal inoculation at gestational day 10. Altogether, these findings suggest that CV-B infection of the fetal thymus may play an important role in the genesis of autoimmune diseases. [less ▲]

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See detailTreg, Th17 and γδ T cells during normal and abortive pregnancy
Polese, Barbara ULg; Gridelet, Virginie ULg; Munaut, Carine ULg et al

Poster (2016, October 14)

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See detailTreg, Th17 and γδ T cells during normal and abortive pregnancy
Polese, Barbara ULg; Gridelet, Virginie ULg; Munaut, Carine ULg et al

Conference (2016, October 14)

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See detailOxytocin in survivors of childhood-onset craniopharyngioma
Daubenbüchel, Anna; Hoffmann, Anika; Eveslage, Maria et al

in Endocrine (2016)

Quality of survival of childhood-onset cranio- pharyngioma patients is frequently impaired by hypotha- lamic involvement or surgical lesions sequelae such as obesity and neuropsychological deficits ... [more ▼]

Quality of survival of childhood-onset cranio- pharyngioma patients is frequently impaired by hypotha- lamic involvement or surgical lesions sequelae such as obesity and neuropsychological deficits. Oxytocin, a pep- tide hormone produced in the hypothalamus and secreted by posterior pituitary gland, plays a major role in regula- tion of behavior and body composition. In a cross- sectional study, oxytocin saliva concentrations were ana- lyzed in 34 long-term craniopharyngioma survivors with and without hypothalamic involvement or treatment- related damage, recruited in the German Childhood Cra- niopharyngioma Registry, and in 73 healthy controls, attending the Craniopharyngioma Support Group Meeting 2014. Oxytocin was measured in saliva of craniophar- yngioma patients and controls before and after standar- dized breakfast and associations with gender, body mass index, hypothalamic involvement, diabetes insipidus, and irradiation were analyzed. Patients with preoperative hypothalamic involvement showed similar oxytocin levels compared to patients without hypothalamic involvement and controls. However, patients with surgical hypotha- lamic lesions grade 1 (anterior hypothalamic area) pre- sented with lower levels (p = 0.017) of oxytocin under fasting condition compared to patients with surgical lesion of posterior hypothalamic areas (grade 2) and patients without hypothalamic lesions (grade 0). Craniophar- yngioma patients’ changes in oxytocin levels before and after breakfast correlated (p = 0.02) with their body mass index. Craniopharyngioma patients continue to secrete oxytocin, especially when anterior hypothalamic areas are not involved or damaged, but oxytocin shows less varia- tion due to nutrition. Oxytocin supplementation should be explored as a therapeutic option in craniopharyngioma patients with hypothalamic obesity and/or behavioral pathologies due to lesions of specific anterior hypotha- lamic areas. Clinical trial number: KRANIOPHAR- YNGEOM 2000/2007(NCT00258453; NCT01272622). [less ▲]

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