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See detailLes arbres à croissance lente embellissent bien plus longtemps que les herbes folles
Geenen, Vincent ULiege

Article for general public (2021)

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See detailModulation of IGF2 expression in the murine thymus and thymic epithelial cells following coxsackie-B4 infection
Michaux, Hélène ULiege; Halouani, Aymen ULiege; Trussart, Charlotte ULiege et al

in Microorganisms (2021), 9(402), 1-21

Coxsackievirus B4 (CV-B4) can infect human and murine thymic epithelial cells (TECs). In a murine TEC cell line, CV-B4 can downregulate the transcription of the insulin-like growth factor 2 (Igf2) gene ... [more ▼]

Coxsackievirus B4 (CV-B4) can infect human and murine thymic epithelial cells (TECs). In a murine TEC cell line, CV-B4 can downregulate the transcription of the insulin-like growth factor 2 (Igf2) gene coding for the self-peptide of the insulin family. In this study, we show that CV-B4 infections of a murine TEC cell line decreased Igf2 P3 promoter activity by targeting a region near the transcription start site; however, the stability of Igf2 transcripts remained unchanged, indicating a regulation of Igf2 transcription. Furthermore, CV-B4 infections decreased STAT3 phosphorylation in vitro. We also showed that mice infected with CV-B4 had an altered expression of Igf2 isoforms as detected in TECs, followed by a decrease in the pro-IGF2 precursor in the thymus. Our study sheds new light on the intrathymic regulation of Igf2 transcription during CV-B4 infections and supports the hypothesis that a viral infection can disrupt central self-tolerance to insulin by decreasing Igf2 transcription in the thymic epithelium. [less ▲]

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See detailThe thymus and the science of Self
Geenen, Vincent ULiege

in Seminars in Immunopathology (2021)

The conventional perception asserts that immunology is the science of ‘discrimination’ between Self and Non-Self. This concept is however no longer tenable as effector cells of the adaptive immune system ... [more ▼]

The conventional perception asserts that immunology is the science of ‘discrimination’ between Self and Non-Self. This concept is however no longer tenable as effector cells of the adaptive immune system are first conditioned to be tolerant to the body’s own antigens, collectively known as Self until now. Only then attain these effectors the responsiveness to Non-Self. The acquisition of this essential state of tolerance to Self occurs for T cells in the thymus, the last major organ of our body that revealed its intricate function in health and disease. The ‘thymus’ as an anatomical notion was first notably documented in Ancient Greece although our present understanding of the organ’s functions was only deciphered commencing in the 1960’s. In the late 80’s, the thymus was identified as the site where clones of cells reactive to Self, termed ‘forbidden’ thymocytes are physically depleted as the result of a process now known as negative selection. The recognition of this mechanism further contributed to the belief that the central rationale of immunology as a science lies in the distinction between Self and Non-Self. This review will discuss the evidence that the thymus serves as a unique lymphoid organ able to instruct T cells to recognize and be tolerant to harmless Self before adopting the capacity to defend the body against potentially injurious Non-Self antigens presented in the context of different challenges from infections to exposure to malignant cells. The emerging insight into the thymus’ cardinal functions now also provides an opportunity to exploit this knowledge to develop novel strategies that specifically prevent or even treat organ-specific autoimmune diseases. [less ▲]

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See detailModified peptides as a novel immunotherapy for rheumatoid arthritis
Araklioti, Eleni ULiege; Herman, Ludivine; Nguyen, Ngoc Quynh Nhu et al

Poster (2020, December)

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See detailLetter to the Editor from Hernan Valdes-Socin: “Genetic Study in a Large Cohort Supported Different Pathogenesis of Graves’ Disease and Hashimoto’s Hypothyroidism”
VALDES SOCIN, Hernan Gonzalo ULiege; Gonzales-Aguilera, Beatriz; Geenen, Vincent ULiege

in Journal of Clinical Endocrinology and Metabolism (2020)

Zhang et al (JCEM 2020) identified several susceptibility genes of Hashimoto and Graves disease in a Chinese Han population. Conversion of Hashimoto Thyroiditis towards Graves’ disease is still an ... [more ▼]

Zhang et al (JCEM 2020) identified several susceptibility genes of Hashimoto and Graves disease in a Chinese Han population. Conversion of Hashimoto Thyroiditis towards Graves’ disease is still an underestimated clinical feature for most clinicians: susceptibility genes for these cases are still unknown.More extensive cohort immunological and genetic studies are necessary to gain insight into these interesting observations. [less ▲]

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See detailModified peptides as a novel immunotherapy for rheumatoid arthritis
Araklioti, Eleni ULiege; Herman, Ludivine; Nguyen, Ngoc Quynh Nhu et al

Poster (2020, June)

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See detailAssessment of thymic output dynamics after in utero infection of mice with coxsakievirus B4
Halouani, Aymen; Jmii, Habib; Bodart, Gwennaëlle ULiege et al

in Frontiers in Immunology (2020), 11

The thymus is the main organ of the lymphatic system, in which T cells undergo a rigorous selection to ensure that their receptors (TCRs) will be functional and will not react against the self. Genes ... [more ▼]

The thymus is the main organ of the lymphatic system, in which T cells undergo a rigorous selection to ensure that their receptors (TCRs) will be functional and will not react against the self. Genes encoding for TCR chains are fragmented and must be rearranged by a process of somatic recombination generating TCR rearrangement excision circles (TRECs). We recently documented coxsackievirus B4 (CV-B4) infection of Swiss albino mouse thymus in the course of in utero transmission. In the current study, we intended to evaluate thymic output in this experimental model. For this purpose, pregnant Swiss albino mice were inoculated with CV-B4 at day 10 or 17 of gestation, and thymus and spleen were sampled from offspring at different time points and then subjected to quantification of TREC molecules and Ptk7 gene expression. Results showed a pronounced effect of in utero CV-B4 infection on the thymus with an increase in the cellularity and, consequently, the weight of the organ. sj and DβTREC analysis, by real-time PCR, revealed a significant decrease following CV-B4 infection compared to controls, a decrease which gets worse as time goes by, both in the thymus and in the periphery. Those observations reflect a disturbance in the export of T cells to the periphery and their accumulation within the thymus. The evaluation of Ptk7 transcripts in the thymus, for its part, showed a decrease in expression, especially following an infection at day 10 of gestation, which supports the hypothesis of T cell accumulation in a mature stage in the thymus. The various effects observed correlate either negatively or positively with the viral load in the thymus and spleen. Disruption in thymic export may indeed interfere with T cell maturation. We speculate that this may lead to a premature release of T cells and the possibility of circulating autoreactive or proliferation-impaired T cell clones. [less ▲]

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See detailHuman chorionic gonadotrophin (hCG): new pleiotropic functions for an "old" hormone during pregnancy
Gridelet, Virginie ULiege; PERRIER d'HAUTERIVE, Sophie ULiege; Polese, Barbara ULiege et al

in Frontiers in Immunology (2020), 11

Human chorionic gonadotrophin (hCG) is the first specific molecule synthesized by the embryo. hcg RNA is transcribed as early as the 8-cell stage and the blastocyst produces the protein before its ... [more ▼]

Human chorionic gonadotrophin (hCG) is the first specific molecule synthesized by the embryo. hcg RNA is transcribed as early as the 8-cell stage and the blastocyst produces the protein before its implantation. hCG in the uterine microenvironment binds with its cognate receptor LHCGR on the endometrial surface. This binding stimulates LIF production and inhibits IL-6 production by epithelial cells of the endometrium. These effects ensure essential help in the preparation of the endometrium for initial embryo implantation. hCG also effects angiogenic and immunomodulatory actions as reported in many articles by our laboratories and other ones. By stimulating angiogenesis and vasculogenesis, hCG provides the placenta with an adequate maternal blood supply and optimal embryo nutrition during the invasion of the uterine endometrium. The immunomodulatory properties of hCG are numerous and important for programming maternal immune tolerance towards the embryo. The reported effects of hCG on uterine NK, Treg and B cells, three major cell populations for the maintenance of pregnancy, demonstrate the role of this embryonic signal as a crucial immune regulator in the course of pregnancy. Human embryo rejection for hCG-related immunological reasons has been studied in different ways, and a sufficient dose of hCG seems to be necessary to maintain maternal tolerance. Different teams have studied the addition of hCG in patients suffering from recurrent miscarriages or implantation failures. HCG could also have a beneficial or a negative impact on autoimmune diseases during pregnancy. In this review, we will discuss the immunological impacts hCG during pregnancy and if this hormone might be used therapeutically. [less ▲]

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See detailHousekeeping Gene Expression in the Fetal and Neonatal Murine Thymus Following Coxsackievirus B4 Infection
Halouani, Aymen ULiege; Jmii, Habib; Michaux, Hélène et al

in Genes (2020), 11

The thymus fulfills the role of T‐cell production and differentiation. Studying transcription factors and genes involved in T‐cell differentiation and maturation during the fetal and neonatal periods is ... [more ▼]

The thymus fulfills the role of T‐cell production and differentiation. Studying transcription factors and genes involved in T‐cell differentiation and maturation during the fetal and neonatal periods is very important. Nevertheless, no studies to date have been interested in evaluating the expressions of housekeeping genes as internal controls to assess the varying expressions of different genes inside this tissue during that period or in the context of viral infection. Thus, we evaluated by real‐time quantitative polymerase chain reaction (qPCR) the expression of the most common internal control genes in the thymus of Swiss albino mice during the fetal and neonatal period, and following in utero infection with Coxsackievirus B4. The stability of expression of these reference genes in different samples was investigated using the geNorm application. Results demonstrated that the expression stability varied greatly between genes. Oaz1 was found to have the highest stability in different stages of development, as well as following Coxsackievirus B4 infection. The current study clearly demonstrated that Oaz1, with very stable expression levels that outperformed other tested housekeeping genes, could be used as a reference gene in the thymus and thymic epithelial cells during development and following Coxsackievirus B4 infection. [less ▲]

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See detailL'influence de Charles Darwin sur la biologie aujourd'hui
Geenen, Vincent ULiege

Scientific conference (2020, February 12)

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See detailL'Héritage[s] de Charles Darwin
Geenen, Vincent ULiege

Scientific conference (2020, January 21)

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See detailLe clonage : quelles limites aujourd'hui et demain ?
Geenen, Vincent ULiege

Scientific conference (2019, December 16)

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See detailA grateful tribute to Professor Helen KORNEVA
Geenen, Vincent ULiege

in Homage Book to Helen Korneva (2019)

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See detailPrograming of the autoimmune diabetogenic response in the thymus during fetal and perinatal life
Geenen, Vincent ULiege; Hober, Didier

in Pediatric Endocrinology Reviews (2019), 17

The presentation of self-peptides in the thymus is responsible both for negative selection of self-reactive T cells emerging during stochastic TCR recombination in fetal life, as well as positive ... [more ▼]

The presentation of self-peptides in the thymus is responsible both for negative selection of self-reactive T cells emerging during stochastic TCR recombination in fetal life, as well as positive selection of self-specific regulatory thymic T (tTreg) cells during and after perinatal life. The combination of these two sequential processes programs central self-tolerance, a fundamental property of the adaptive immune system. A defect in intrathymic self-presentation, either genetic or acquired, is the earliest event in the pathogenesis of autoimmunity already during fetal development. This defect is necessary but not sufficient for the appearance of a classical autoimmune disease like type 1 diabetes (T1D). Environmental factors are required for activation of the diabetogenic autoimmune response that targets insulin-secreting β cells in pancreatic Langerhans’ islets. Based on epidemiological studies, viral infections have been suspected for a long time to be one of those environmental factors. In this Debate article, we present a series of experimental data that support the hypothesis that, following vertical transplacental transfer, viruses might infect the fetal thymus and disturb already in utero central self-tolerance orchestrated by this organ. [less ▲]

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See detail"Petits" inconvénients de l'immunothérapie anti-tumorale
Geenen, Vincent ULiege

Scientific conference (2019, November 29)

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See detailVers un nouveau type de vaccin contre le diabète de type 1 ?
Geenen, Vincent ULiege

Learning material (2019)

Notre corps héberge un système de défenses immunitaires qui nous protègent contre les multiples agressions infectieuses et qui surveillent la survenue de cellules cancéreuses pour les éliminer ... [more ▼]

Notre corps héberge un système de défenses immunitaires qui nous protègent contre les multiples agressions infectieuses et qui surveillent la survenue de cellules cancéreuses pour les éliminer. Suite aux travaux d’Edward Jenner en Angleterre et de Louis Pasteur en France, cette propriété d’immunogénicité a permis l’avènement de la vaccination contre beaucoup de maladies infectieuses qui reste un des plus grands triomphes de la médecine. Toutefois, avant de nous défendre contre le Non-Soi, le système immunitaire doit être éduqué à ne pas agresser les organes du corps qui l’abrite et doit être rendu tolérant vis-à-vis du Soi. [less ▲]

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See detailVers un vaccin belge contre le diabète ?
Geenen, Vincent ULiege

Article for general public (2019)

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See detailChapter 1 - History of the thymus: from a vestigial organ to the programming of immunological self-tolerance
Geenen, Vincent ULiege

in Passos, Gerald (Ed.) Thymus Transcriptome and Cell Biology (2019)

This introductive chapter presents the most important disruptions of con- cepts concerning the thymus since its discovery in Antique Greece. For centuries, the thymus was considered as a vestigial organ ... [more ▼]

This introductive chapter presents the most important disruptions of con- cepts concerning the thymus since its discovery in Antique Greece. For centuries, the thymus was considered as a vestigial organ, and its role in T-cell differentiation was proposed only in the 1960s. Most recent studies attribute to the thymus an essential and unique role in programming central immunological self-tolerance. The basic mechanism implicated in this function is the transcription in the thymic epithelium of genes encoding precursors of neuroendocrine-related and tissue- restricted self-peptides. Their processing leads to the presentation of self-antigens by the major histocompatibility complex (MHC) machinery expressed by thymic epithelial and dendritic cells. Already during foetal life, this presentation promotes negative selection of T lymphocytes harbouring a receptor with high affinity for MHC/self-peptide complexes. Mainly after birth, this presentation also drives the generation of regulatory T cells specific for these complexes. Numerous studies, as well as the identification of Aire and Fezf2 genes, have shown that a thymus defect plays a crucial role in the development of autoimmunity. The discovery of the cen- tral tolerogenic action of the thymus revolutionized the whole field of immunology, and such knowledge will pave the way for innovative tolerogenic therapies against autoimmunity, the so heavy tribute paid by mankind for the extreme diversity and efficiency of adaptive immunity. [less ▲]

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