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

Book published by Presses Universitaires de Liège (2016)

Cet ouvrage concis s'intéresse au thymus, un organe dont la fonction a échappé si longtemps au monde de la science que d'aucuns le considèrent encore aujourd'hui comme un vestige de l'évolution. Vous le ... [more ▼]

Cet ouvrage concis s'intéresse au thymus, un organe dont la fonction a échappé si longtemps au monde de la science que d'aucuns le considèrent encore aujourd'hui comme un vestige de l'évolution. Vous le connaissez néanmoins très bien car vous avez certainement consommé de très savoureux 'ris de veau' qui sont la dénomination culinaire du thymus de cet animal. Ce n'est qu'au cours des 60 dernières années environ que cet organe a livré un à un ses secrets les plus intimes jusqu'à occuper la place essentielle de 'petit cerveau' de notre système de défenses immunitaires. Cet essai concerne donc aussi l’immunologie, la science qui étudie les mécanismes de notre système de défenses, contre les agressions infectieuses surtout, en un mot l’immunité. Dès la fondation de cette nouvelle science à la fin du XIXe siècle, les immunologistes ont été confrontés à cet important paradoxe: comment notre système immunitaire, capable de réagir contre une multitude d’agents étrangers (ce qui est désigné comme le ‘non-soi’), est-il heureusement incapable en conditions normales d’agresser l’organisme qui l’héberge (le ‘soi’) ? Cette impossibilité du système immunitaire de réagir contre le ‘soi’ s’appelle la ‘tolérance immunitaire’ et elle est devenue aujourd’hui la pierre angulaire du fonctionnement normal de ce système. La rupture de cette tolérance est à l’origine des maladies dites ‘auto-immunes’. Il en existe environ 70 dont les plus connues sont le diabète juvénile insulino-dépendant (diabète de type 1) qui frappe les enfants et les jeunes adolescents, la plupart des affections de la glande thyroïde, la sclérose en plaques, le psoriasis et la polyarthrite rhumatoïde. J’ai souhaité inviter le lecteur à pénétrer dans un monde qui était encore presque inconnu il y a moins de soixante ans, celui du thymus qui peut être qualifié aujourd’hui sinon de ‘cerveau’, au moins de programmeur central de la tolérance immunitaire. Les travaux menés par mon groupe à l’Université de Liège ont établi que le thymus constitue un carrefour crucial entre les trois grands systèmes de communication intercellulaire des espèces vivantes, les systèmes nerveux, endocrine et immunitaire. Ils ont démontré que le thymus joue un rôle unique dans la programmation de la tolérance immunitaire vis-à-vis des systèmes nerveux et endocrine. Ces études ont aussi établi qu’un dysfonctionnement du thymus joue un rôle moteur dans le développement des maladies auto-immunes spécifiques des glandes endocrines. En un mot, c’est d’abord le thymus qui est malade et non les organes touchés par le processus auto-immun pathogène qui résulte de cette pathologie du thymus. Mon plus vif espoir aujourd’hui est que la découverte de ce nouveau concept se traduise un jour par l’invention d’un nouveau type de vaccination contre le diabète des enfants et des adolescents. Quelles sont les raisons qui ont motivé ma candidature au Prix littéraire Prince Alexandre de Belgique 2014. 1° La première était de témoigner ma reconnaissance à l’égard de la Fondation cardiologique Princesse Lilian qui a joué un rôle déterminant dans l’orientation de ma carrière de médecin-chercheur. En effet, cette Fondation a organisé en 1984 à Bruxelles un symposium international consacré au contrôle exercé par le système nerveux sur le système immunitaire. Mon promoteur, le regretté Pr Paul Franchimont, avait assisté à ce symposium et me conseilla vivement d’essayer de développer des activités de recherches dans ce tout nouveau domaine. C’est dans ce même esprit de reconnaissance à la Fondation Princesse Lilian que j’ai proposé que la chaire internationale du même nom soit confiée en 2015 à mon confrère allemand, lui aussi spécialiste du thymus, le Pr Bruno Kyewski de l’Institut allemand de la recherche contre le cancer à Heidelberg en Allemagne. Cette proposition a été acceptée et la leçon inaugurale de cette chaire a eu lieu le 16 mars 2015 en la Grande Salle Académique de l’Université de Liège. 2° Mon goût pour la littérature, qu’elle soit romancière, historique, scientifique ou philosophique, constitue incontestablement la deuxième raison de ma candidature au Prix Prince Alexandre. Combien de fois n’ai-je lu une œuvre littéraire en m’interrogeant si je serais capable moi-même d’écrire un jour un livre ? C’est aussi en me plongeant dans la littérature que j’ai vécu les plus beaux voyages initiatiques de la pensée. 3° Une autre raison essentielle qui m’a poussé à rédiger mes « Voyage(s) à travers le thymus » est la suivante. L’équipe de recherche que j’anime au Centre d’Immunologie du GIGA de Liège a contribué à mettre au jour un phénomène essentiel de la vie qui est apparu avec le premier thymus il y a environ 450 millions d’années chez les poissons cartilagineux comme la raie ou le requin. Cette ‘découverte’ d’un secret inouï de la vie suscite alors en vous une sensation d’émerveillement du même ordre que l’émotion qui vous étreint quand vous écoutez l’Oratorio de Noël ou la Passion selon Saint-Mathieu de Jean-Sébastien Bach, quand vous regardez un tableau de Piero de la Francesca, ou quand vous contemplez une merveille de la Nature comme le Grand Canyon du Colorado ou le lever du soleil sur Massif du Hoggar depuis l’ermitage du Père de Foucault à l’Assekrem. Vous pouvez très bien vivre seul un pareil émerveillement mais le premier désir que vous ressentez au fond de vous-même est de le partager avec vos proches. Ce désir irrésistible a joué lui aussi un rôle déterminant dans ma décision de consacrer la majeure partie de mes soirées de l'été 2014 à écrire ce texte et, surtout, à le rédiger de manière compréhensible pour toutes et tous. Et c’est là que réside la plus grande difficulté car, comme le disait Albert Einstein, « Si vous ne pouvez expliquer un concept à un enfant de six ans, c'est que vous ne le comprenez pas complètement ». 4° Enfin, les trente-cinq années de ma vie de médecin engagé dans la recherche ont exercé un impact considérable sur ma propre conception de la vie et de ses innombrables mystères. Mon essai se clôture par un témoignage personnel décrivant comment ces différents voyages ont nourri ma réflexion à propos des rapports entre la science et la foi. J’ai tenté d’expliquer qu’il était encore possible aujourd’hui de rester chrétien en devenant un scientifique quelque peu écouté, comment mes vies professionnelle et spirituelle pouvaient se nourrir l’une de l’autre tout en respectant leur indépendance. [less ▲]

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See detailThymectomy in myasthenia gravis: removal of the defective 'sick' organ?
Geenen, Vincent ULg

E-print/Working paper (2016)

As evidenced by this randomized trial, thymectomy clearly improved clinical status of patients with nonthymomatous myasthenia gravis (MG) and this study ends a very long controversy about the interest of ... [more ▼]

As evidenced by this randomized trial, thymectomy clearly improved clinical status of patients with nonthymomatous myasthenia gravis (MG) and this study ends a very long controversy about the interest of this surgical procedure mainly based on previous empirical observations. Although they are not discussed in this important paper, a series of experimental arguments reviewed in joint references argue for the idea that the clinical benefit of thymectomy is primarily due to the removal of the organ primarily implicated in MG pathophysiology. The thymus plays a central role in programming central immunological self-tolerance [1,2], and a thymus dysfunction is a primary event in the development of organ-specific autoimmunity [3,4]. It is therefore not surprising that the surgical removal of the primary 'sick' organ contributes to improve clinical outcomes and to reduce immunosuppressive therapy in MG patients. References: 1. Kamradt T, Mitchison NA. N Engl J Med 2001; 344:655-64. 2. Kyewski B, Klein L. Annu Rev Immunol 2006; 24:571-606. 3. Giraud M, Taubert R, Vandiedonck C, et al. Nature 2007; 448:934-7. 4. Geenen V, Bodart G, Henry S, et al. Front Neurosc 2013; 7:art 187. [less ▲]

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See detailDrug-induced thyroid dysfunction
Geenen, Vincent ULg

Conference (2016, April 16)

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See detailThymus and Type 1 diabetes: Where are we now?
Geenen, Vincent ULg

Scientific conference (2016, March 24)

Our studies have demonstrated that the thymus programs central self-tolerance to neuroendocrine functions through transcription of neuroendocrine-related genes in thymic epithelial cells (TECs). However ... [more ▼]

Our studies have demonstrated that the thymus programs central self-tolerance to neuroendocrine functions through transcription of neuroendocrine-related genes in thymic epithelial cells (TECs). However, thymic neuroendocrine precursors are not secreted but processed as the source of neuroendocrine self-antigens that are presented by thymic proteins of the major histocompatibility complex (MHC). This process, highly specific of the thymus, has allowed an integrated and harmonious coevolution of the neuroendocrine and immune systems when recombination-activating genes and the subsequent adaptive immune response have emerged in cartilaginous fishes some 450-500 millions years ago. All the members of the insulin gene family are expressed in murine TECs under the control of AutoImmune Regulator (AIRE) according a precise hierarchy: Igf2 >Igf1>Ins2>Ins1. Igf2 transcription is defective in TECs of autoimmune diabetes-prone BB rats, and tolerance to insulin is severely impaired in Igf2-/- mice as well as in Igf2-loxP/Foxn1-cre mice with Igf2 deletion targeted in TECs. In addition, the diabetogenic coxsackievirus B4 (CV-B4) is able to persistently infect human and murine TECs and to inhibit Igf2 transcription and IGF-2 synthesis in a murine medullary TEC line (coolaboration with D. Hober, Laboratory of Virology, CHRU and University of Lille 2, France). These studies show that: 1° IGF-2 is the dominant tolerogenic precursor of the family and mediates cross-tolerance to insulin; 2° a thymus dysfunction plays a crucial role in the development of the diabetogenic autoimmune response; and 3° a thymic infection by CV-B4 is implicated in type 1 diabetes (T1D) pathogenesis. Most probably due to its very low level of expression in the thymus, the protein insulin is highly immunogenic and is the primary autoantigen tackled in T1D. On the basis of the tolerogenic properties of IGF-2, we are currently working on the development of a negative/tolerogenic self-vaccine against T1D. [less ▲]

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See detailVoyage[s] through the thymus, the small central 'brain' of the adaptive immune system
Geenen, Vincent ULg

Scientific conference (2016, March 24)

Our studies have demonstrated that the thymus programs central self-tolerance to neuroendocrine functions through transcription of neuroendocrine-related genes in thymic epithelial cells (TECs). However ... [more ▼]

Our studies have demonstrated that the thymus programs central self-tolerance to neuroendocrine functions through transcription of neuroendocrine-related genes in thymic epithelial cells (TECs). However, thymic neuroendocrine precursors are not secreted but processed as the source of neuroendocrine self-antigens that are presented by thymic proteins of the major histocompatibility complex (MHC). This process, highly specific of the thymus, has allowed an integrated and harmonious coevolution of the neuroendocrine and immune systems when recombination-activating genes and the subsequent adaptive immune response have emerged in cartilaginous fishes some 450-500 millions years ago. All the members of the insulin gene family are expressed in murine TECs under the control of AutoImmune Regulator (AIRE) according a precise hierarchy: Igf2 >Igf1>Ins2>Ins1. Igf2 transcription is defective in TECs of autoimmune diabetes-prone BB rats, and tolerance to insulin is severely impaired in Igf2-/- mice as well as in Igf2-loxP/Foxn1-cre mice with Igf2 deletion targeted in TECs. In addition, the diabetogenic coxsackievirus B4 (CV-B4) is able to persistently infect human and murine TECs and to inhibit Igf2 transcription and IGF-2 synthesis in a murine medullary TEC line (coolaboration with D. Hober, Laboratory of Virology, CHRU and University of Lille 2, France). These studies show that: 1° IGF-2 is the dominant tolerogenic precursor of the family and mediates cross-tolerance to insulin; 2° a thymus dysfunction plays a crucial role in the development of the diabetogenic autoimmune response; and 3° a thymic infection by CV-B4 is implicated in type 1 diabetes (T1D) pathogenesis. Most probably due to its very low level of expression in the thymus, the protein insulin is highly immunogenic and is the primary autoantigen tackled in T1D. On the basis of the tolerogenic properties of IGF-2, we are currently working on the development of a negative/tolerogenic self-vaccine against T1D. [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, January 25)

Detailed reference viewed: 32 (6 ULg)
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See detailSwitch from Hashimoto Thyroiditis (HT) to Graves Basedow (GB) disease : a controlled study in a series of 15 patients
Maiga, I; BETEA, Daniela ULg; Geenen, Vincent ULg et al

in Abstract book - 20th Annual Congress of the Belgian Society of Internal Medicine (2015, December)

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See detailThe central role of the thymus in the programming of immunological tolerance to neuroendocrine self: Implications for the pathogenesis of autoimmune diseases.

Geenen, Vincent ULg

Conference (2015, June)

Our studies have demonstrated that the thymus programs central self-tolerance to neuroendocrine functions through transcription of neuroendocrine-related genes in thymic epithelial cells (TECs). However ... [more ▼]

Our studies have demonstrated that the thymus programs central self-tolerance to neuroendocrine functions through transcription of neuroendocrine-related genes in thymic epithelial cells (TECs). However, thymic neuroendocrine precursors are not secreted but processed as the source of neuroendocrine self-antigens that are presented by thymic proteins of the major histocompatibility complex (MHC). This process, highly specific of the thymus, has allowed an integrated and harmonious coevolution of the neuroendocrine and immune systems when recombination-activating genes and the subsequent adaptive immune response have emerged in cartilaginous fishes some 450-500 millions years ago. All the members of the insulin gene family are expressed in murine TECs under the control of AutoImmune Regulator (AIRE) according a precise hierarchy: Igf2 >Igf1>Ins2>Ins1. Igf2 transcription is defective in TECs of autoimmune diabetes-prone BB rats, and tolerance to insulin is severely impaired in Igf2-/- mice as well as in Igf2-loxP/Foxn1-cre mice with Igf2 deletion targeted in TECs. In addition, the diabetogenic coxsackievirus B4 (CV-B4) is able to persistently infect human and murine TECs and to inhibit Igf2 transcription and IGF-2 synthesis in a murine medullary TEC line (coolaboration with D. Hober, Laboratory of Virology, CHRU and University of Lille 2, France). These studies show that: 1° IGF-2 is the dominant tolerogenic precursor of the family and mediates cross-tolerance to insulin; 2° a thymus dysfunction plays a crucial role in the development of the diabetogenic autoimmune response; and 3° a thymic infection by CV-B4 is implicated in type 1 diabetes (T1D) pathogenesis. Most probably due to its very low level of expression in the thymus, the protein insulin is highly immunogenic and is the primary autoantigen tackled in T1D. On the basis of the tolerogenic properties of IGF-2, we are currently working on the development of a negative/tolerogenic self-vaccine against T1D. [less ▲]

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See detailL'école liégeoise de physiologie aux 19e et 20e siècles
Geenen, Vincent ULg

in Histoire des Sciences Médicales (2015), XLIX(2), 209-218

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See detailAdditional intranasal oxytocin to escitalopram improves depressive symptoms in resistant depression: An open trial.
Scantamburlo, Gabrielle ULg; Hansenne, Michel ULg; Geenen, Vincent ULg et al

in European psychiatry : the journal of the Association of European Psychiatrists (2015), 30(1), 65-68

The aim of this open trial was to assess the antidepressant/anxiolytic effects of oxytocin used as an adjunct to antidepressant in treatment-resistant depression. Fourteen patients, who have not responded ... [more ▼]

The aim of this open trial was to assess the antidepressant/anxiolytic effects of oxytocin used as an adjunct to antidepressant in treatment-resistant depression. Fourteen patients, who have not responded to 40mg of escitalopram, received intranasal synthetic oxytocin during 4 weeks, in association with antidepressant. This is the first open trial study suggesting OT in association with escitalopram significantly reduced scores on Hamilton Depression Rating Scale. [less ▲]

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See detailIntroduction à l'embryologie animale
Geenen, Vincent ULg

Learning material (2015)

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