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See detailThe presentation of neuroendocrine self-peptides in the thymus: An essential event for individual life and vertebrate survival
Geenen, Vincent ULiege; Trussart, Charlotte; Michaux, Hélène et al

in Annals of the New York Academy of Sciences (2019)

Confirming Burnet’s early hypothesis, elimination of self-reactive T cells in the thymus was demonstrated in the late 80’s and an important question immediately arose about the nature of the immune self ... [more ▼]

Confirming Burnet’s early hypothesis, elimination of self-reactive T cells in the thymus was demonstrated in the late 80’s and an important question immediately arose about the nature of the immune self expressed in the thymus. Many genes encoding neuroendocrine-related and tissue-restricted antigens (TRAs) are transcribed in thymic epithelial cells (TECs). They are then processed for presentation by proteins of the major histocompatibility complex (MHC) expressed by TECs and thymic dendritic cells (DCs). MHC presentation of self-peptides in the thymus programs self-tolerance by two complementary mechanisms: 1° Negative selection of self-reactive ‘forbidden’ T-cell clones starting already in fetal life, and 2° generation of self-specific thymic T regulatory (tTreg) cells, mainly after birth. Many studies, including the discovery of the AutoImmune REgulator (AIRE) and fasciculation and elongation protein zeta family zinc finger (FEZF2) proteins, have shown that a defect in thymus central self-tolerance is the earliest event promoting autoimmunity. AIRE and FEZF2 control the level of transcription of many neuroendocrine self-peptides and TRAs in thymic epithelium. Furthermore, Aire and Fezf2 mutations are associated with development of autoimmunity in peripheral organs. The discovery of the intrathymic presentation of self-peptides has revolutionized our knowledge of immunology and is opening novel avenues for prevention/treatment of autoimmunity. [less ▲]

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See detailGrowth hormone (GH) deficient mice with GHRH ablation are severely deficient in vaccine and immune responses against Streptococcus pneumoniae
Farhat, Khalil; Bodart, Gwennaëlle ULiege; Moutschen, Michel ULiege et al

in Acta Clinica Belgica (2018, December), 73(6 (Suppl.2)),

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See detailGrowth hormone (GH) deficient mice with GHRH ablation are severely deficient in vaccine and immune responses against Streptococcus pneumoniae
Farhat, Khalil; Bodart, Gwennaëlle ULiege; Charlet-Renard, Jeanne de Chantal ULiege et al

in Frontiers in Immunology (2018), 9

The precise impact of the somatotrope axis upon the immune system is still highly debated. We have previously shown that mice with generalized ablation of growth hormone (GH) releasing hormone (GHRH) gene ... [more ▼]

The precise impact of the somatotrope axis upon the immune system is still highly debated. We have previously shown that mice with generalized ablation of growth hormone (GH) releasing hormone (GHRH) gene (Ghrh−/−) have normal thymus and T-cell development, but present a marked spleen atrophy and B-cell lymphopenia. Therefore, in this paper we have investigated vaccinal and anti-infectious responses of Ghrh−/− mice against S. pneumoniae, a pathogen carrying T-independent antigens. Ghrh−/− mice were unable to trigger production of specific IgM after vaccination with either native pneumococcal polysaccharides (PPS, PPV23) or protein-PPS conjugate (PCV13). GH supplementation of Ghrh−/− mice restored IgM response to PPV23 vaccine but not to PCV13 suggesting that GH could exert a specific impact on the spleen marginal zone that is strongly implicated in T-independent response against pneumococcal polysaccharides. As expected, after administration of low dose of S. pneumoniae, wild type (WT) completely cleared bacteria after 24 h. In marked contrast, Ghrh−/− mice exhibited a dramatic susceptibility to S. pneumoniae infection with a time-dependent increase in lung bacterial load and a lethal bacteraemia already after 24 h. Lungs of infected Ghrh−/− mice were massively infiltrated by inflammatory macrophages and neutrophils, while lung B cells were markedly decreased. The inflammatory transcripts signature was significantly elevated in Ghrh−/− mice. In this animal model, the somatotrope GHRH/GH/IGF1 axis plays a vital and unsuspected role in vaccine and immunological defense against S. pneumoniae. [less ▲]

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See detailHistorical introduction to the history of the thymus and the concept of immune self-tolerance
Geenen, Vincent ULiege; Martens, Henri ULiege

Conference (2018, September)

The name ‘thymus’ first appeared in Galen’s manuscripts (±160 AD) and was so named because of its morphological analogy with the leaf of Thymus cunila. For centuries however, this organ was considered ... [more ▼]

The name ‘thymus’ first appeared in Galen’s manuscripts (±160 AD) and was so named because of its morphological analogy with the leaf of Thymus cunila. For centuries however, this organ was considered only as a vestigial organ that served as a cushion between the sternum and basal blood vessels, and then involuted after puberty. In the late 50’s, JFAP Miller discovered that the thymus was the site for development of a special population of immune cells, the thymo-dependent T lymphocytes. In concordance with P Ehrlich’s early concept of ‘horror autoxicus’, FM Burnet predicted in 1962 that the thymus should play a crucial role in the elimination of developing lymphocytes with potential reactivity against the ‘self’ (‘forbidden’ T cell clones). This theory of intrathymic negative selection of self-reactive T cells was finally demonstrated in late 80’s through the elegant studies in the laboratories of N Le Douarin (Nogent-sur-Marne), P Marrack and J Kappler (Denver), HR Mac Donald (Lausanne) and H von Boehmer (Basel). In the same time, an important question raised about the biochemical nature of the ‘self’ expressed in thymic microenvironment. Our laboratory established that thymic epithelial cells (TECs) from different species transcribe dominant genes of many neuroendocrine families (OT for neurohypophysial family, NKA for tachykinins, NT for neuromedins and IGF-2 for insulin family). However, after transcription, neuroendocrine precursors are not linked to classic (neuro)secretion. Their processing is the source of neuroendocrine self-peptides that are presented by proteins of the major histocompatibility complex (MHC) expressed by TECs and thymic dendritic cells. Through this unique process, already during fetal development, the thymus programs central self-tolerance of the adaptive immune system to neuroendocrine functions and this was an absolute necessity after emergence of this novel form of immunity generating the diversity of antigen recognition some 470 millions years ago. The laboratory of the late B Kyewski further demonstrated the central role of the thymus in central immune tolerance to almost all peripheral tissues. Several laboratories then addressed the logical hypothesis that a defect in the tolerogenic function of the thymus could be a primary event promoting the development of autoimmunity. Several experimental data argued for this assumption and the question was definitively solved with the identification of the AutoImmuneREgulator gene. AIRE controls the level of transcription of many (but not all) tissue specific self-peptides in medullary TECs and AIRE mutations (or Aire ablation) is associated with the development of autoimmunity tackling many peripheral organs. More recently, the Fezf2 gene, already known to be involved in neuronal development, was shown to be expressed in TECs and to regulate the transcription level of Aire-independent genes also coding for tissue specific self-antigens. As stated by several authors, the discovery of the central tolerogenic of the thymus revolutionized the whole field of immunology. Undoubtedly, this novel knowledge will pave the way for innovative tolerogenic therapies aiming to prevent and treat autoimmunity, the so heavy tribute paid by all mankind for the extreme diversity and efficiency of adaptive immunity. (Vincent Geenen is research director at F.S.R.-NFSR of Belgium. Supported by F.S.R.-NFSR, Wallonia, the Federation Wallonia-Brussels, European Union, JDRF, and the Fonds Léon Fredericq of Liège University Hospital.) References 1. Martens H, Goxe B and Geenen V. The thymic repertoire of neuroendocrine self-antigens: physiological implications in, T cell life and death. Immunol Today 1996; 17:312-7. 2. Geenen V et al. Programming of neuroendocrine self in the thymus and its defect in the development of neuroendocrine autoimmunity. Front Neurosci 2013; 7: article 187 - doi: 10.3389/fnins.2013.00187. 3. Geenen V. Histoire du thymus : d’un organe vestigial à la programmation de la tolérance immunitaire. Med Sci 2017; 33:653-63. [less ▲]

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See detailThe severe deficiency of the somatotrope GHRH/GH/IGF1 axis of Ghrh-/- mice is associated with an important splenic atrophy and relative B lymphopenia
Bodart, Gwennaëlle ULiege; Farhat, Khalil ULiege; Charlet-Renard, Jeanne de Chantal ULiege et al

in Frontiers in Endocrinology (2018), 9(Art. 296),

A debate is still open about the precise control exerted by the somatotrope GH-releasing hormone (GHRH)/growth hormone (GH)/insulin-like growth factor 1 axis on the immune system. The objective of this ... [more ▼]

A debate is still open about the precise control exerted by the somatotrope GH-releasing hormone (GHRH)/growth hormone (GH)/insulin-like growth factor 1 axis on the immune system. The objective of this study was to directly address this question through the use of Ghrh−/− mice that exhibit a severe deficiency of their somatotrope axis. After control backcross studies and normalization for the reduced global weight of transgenic mice, no difference in weight and cellularity of the thymus was observed in Ghrh−/− mice when compared with C57BL/6 wild-type (WT) control mice. Similarly, no significant change was observed in frequency and number of thymic T cell subsets. In the periphery, Ghrh−/− mice exhibited an increase in T cell proportion associated with a higher frequency of sjTREC and naïve T cells. However, all Ghrh−/− mice displayed an absolute and relative splenic atrophy, in parallel with a decrease in B cell percentage. GH supplementation of transgenic mice for 6 weeks induced a significant increase in their global as well as absolute and relative splenic weight. Interestingly, the classical thymus involution following dexamethasone administration was shown to recover in WT mice more quickly than in mutant mice. Altogether, these data show that the severe somatotrope deficiency of Ghrh−/− mice essentially impacts the spleen and B compart- ment of the adaptive immune system, while it only marginally affects thymic function and T cell development. [less ▲]

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See detailImpact of high magnification sperm selection on neonatal outcomes: a retrospective study.
GASPARD, Olivier ULiege; VANDERZWALMEN, Pierre; WIRLEITNER, Barbara et al

in Journal of Assisted Reproduction and Genetics (2018), 35(6), 1113-1121

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See detailGHRH-deleted Mice Are Severely Deficient in Vaccine And Immunological Responses Against Streptococcus Pneumoniae
Farhat, Khalil ULiege; Bodart, Gwennaëlle ULiege; Desmet, Christophe ULiege et al

Conference (2018, March 20)

Background and objective of the work. Ghrh-/- mice with a severe deficiency of their somatotrope GHRH/GH/IGF1 axis (1) are resistant to experimental allergic encephalomyelitis (2). In basal conditions ... [more ▼]

Background and objective of the work. Ghrh-/- mice with a severe deficiency of their somatotrope GHRH/GH/IGF1 axis (1) are resistant to experimental allergic encephalomyelitis (2). In basal conditions, thymus and T-cell development are not severely affected but a marked spleen atrophy and B-cell lymphopenia were constantly observed (3). Therefore, we investigated vaccinal and anti-infectious responses of Ghrh-/- mice against S.pneumoniae, a T-independent pathogen. Results. Transgenic mice were unable to trigger production of specific IgM after vaccination with either native pneumococcal polysaccharides (PPS, Pnx23) or protein-PPS conjugate (Prev13). GH treatment of Ghrh-/- mice restored IgM response to Pnx23 vaccine but not to Prev13 suggesting that GH exerts a significant impact on the spleen marginal zone that is strongly implicated in T-independent immunological response to pneumococcal polysaccharides. After intranasal instillation of a non-lethal dose of S.pneumoniae, Ghrh-/- mice exhibited a dramatic susceptibility with a time-dependent increase in lung bacterial load, a bacteremia already after 24h, and a survival limit of 48-72h. In marked contrast, WT and heterozygote mice completely cleared S.pneumoniae infection after 24h. Lungs of infected Ghrh-/- mice were massively infiltrated by inflammatory macrophages, while lung B cells were markedly decreased. Transcription of Ifng, Il10, Cd40, and Cxcl9 was highly increased in the lungs of infected Ghrh-/- mice, whereas Tgfb and Iggj transcripts were unchanged. Resistance of Ghrh-/- mice to infection by influenzavirus H1N1 (a T-dependent antigen) was normal or slightly decreased. Conclusion. This animal model shows that the somatotrope GHRH/GH/IGF1 axis plays a vital and unsuspected role in the vaccine and immunological defense against S.pneumoniae. [less ▲]

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See detailAccumulation of IL-17+ Vgamma6+ gamma-delta T cells in pregnant mice is not associated with spontaneous abortion
Polese, Barbara ULiege; Gridelet, Virginie ULiege; Perrier d'Hauterive, Sophie ULiege et al

in Clinical and Translational Immunology (2018), 7

Introduction. Pregnancy is an immune paradox. While the immune system is required for embryo implantation, placental development and progression of gestation, excessive inflammation is associated with ... [more ▼]

Introduction. Pregnancy is an immune paradox. While the immune system is required for embryo implantation, placental development and progression of gestation, excessive inflammation is associated with pregnancy failure. Similarly, the cytokine IL-17A plays an important role in defence against extracellular pathogens, but its dysregulation can lead to pathogenic inflammation and tissue damage. Although expression of IL-17 has been reported during pregnancy, the cellular source of this cytokine and its relevance to gestation are not clear. Objectives. Here we define the kinetics and cellular source of IL-17A in the uterus during healthy and abortion-prone murine pregnancy. Methods. The CBA/J x DBA/2J abortion-prone mating was used and compared to CBA/J x BALB/c control mating. Results. We demonstrate that, irrespective of gestational health, the number of IL-17-producing cells peaks during midterm pregnancy and is largely derived from the gd T-cell lineage. We identify cd T, Th17, CD8 T and NKT cells as the cellular source of IL-17A in pregnant mice. Furthermore, we positively identify the Vc6+ subset of uterine gd T cells as the main producer of IL-17A during both healthy pregnancy and abortive pregnancy. Conclusions. To conclude, the accumulation of uterine IL-17+ innate-like T cells appears not to adversely impact the developing foetus. Collectively, our results show that IL-17+ gd T cells are present in the uterus throughout the course of normal gestation and therefore may play an important role in healthy pregnancy. Keywords: abortion, gamma delta T cells, interleukin-17, pregnancy. [less ▲]

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See detailImmunosenescence and infectious diseases
Moutschen, Michel ULiege; Martens, Henri ULiege; Geenen, Vincent ULiege

in Michel, Jean-Pierre; Beattie, B. Lynn; Martin, Finbarr C. (Eds.) et al Oxford Textbook of Geriatric Medicine - 3rd Edition (2017)

In this chapter, we will briefly review the principal modes of interactions taking place between the host’s immune system and the principal groups of microorganisms. We will focus on the way these modes ... [more ▼]

In this chapter, we will briefly review the principal modes of interactions taking place between the host’s immune system and the principal groups of microorganisms. We will focus on the way these modes of interactions are modified by intrinsic and extrinsic factors associated with ageing. As described in Chapter 45, one of the principal features of immunosenescence is linked to thymus involution with subsequent loss of diversity of the repertoire of naïve T-cells. This has a major impact on the adaptative immune responses developed against newly encountered pathogens. Interestingly, more ubiquitous mechanisms associated with the ageing process itself could also have an impact on innate immunity. Defective autophagy impairs the clearance of intracellular pathogens and age-related defects of the ubiquitination-proteasome pathway concur to blunt antiviral responses. In summary, healthy ageing is associated with subtle impairments of innate and adaptive immunity directed against all groups of pathogens. The presence of comorbid states often exerts a synergistic effect on the susceptibility to infectious diseases. [less ▲]

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See detailExploring the link between innate immune activation and thymic function by measuring sCD14 and TRECs in HIV patients living in Belgium
DE VOEGHT, Adrien ULiege; Martens, Henri ULiege; RENARD, Jeanne de Chantal ULiege et al

in PLoS ONE (2017)

Microbial translocation is now viewed as a central event in the pathogenesis of chronic inflammation during HIV infection. Thymic function failure is another crucial factor involved in HIV disease ... [more ▼]

Microbial translocation is now viewed as a central event in the pathogenesis of chronic inflammation during HIV infection. Thymic function failure is another crucial factor involved in HIV disease progression. The goal of this study was to explore the hypothesis of potential links between microbial translocation and thymic function in HIV-1 patients living in Belgium. The extent of microbial translocation was assessed through the measurement of soluble CD14 (sCD14). T-cell receptor excision circles (sjTRECs and dβTRECs) were used as a measure of thymic function. Data were collected from 75 HIV-infected patients. Simple and complex linear regressions were done to analyze the link between these two processes. We found a statistically relevant negative correlation between thymopoiesis (sjTREC) and sCD14 level (p = 0.004). These results suggest a link between thymic function failure, microbial translocation and innate immune activation. [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, Gwennaëlle ULiege; RENARD, Jeanne de Chantal ULiege 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 ULiege; Bodart, Gwennaëlle ULiege; 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 detailMechanisms of Igf2 inhibition in thymic epithelial cells infected with CVB4 E2
Michaux, Hélène ULiege; Charlet-Renard, Chantal; Martens, Henri ULiege et al

Poster (2017, March 12)

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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 ULiege; Farhat, Khalil; Charlet-Renard, Jeanne de Chantal ULiege 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 detailA surprising and dramatic neuroendocrine-immune phenotype of mice deficient in Growth Hormone-Releasing Hormone (GHRH)
Farhat, Khalil; Bodart, Gwennaelle; Martens, Henri ULiege 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 ULiege; Bodart, Gwennaëlle ULiege; Desmet, Christophe ULiege 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 ULiege; Gridelet, Virginie ULiege; Munaut, Carine ULiege et al

Poster (2016, October 14)

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

Conference (2016, October 14)

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