References of "Martens, Henri"
     in
Bookmark and Share    
Full Text
Peer Reviewed
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 ▲]

Detailed reference viewed: 25 (3 ULg)
Peer Reviewed
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)

Detailed reference viewed: 14 (3 ULg)
Peer Reviewed
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)

Detailed reference viewed: 23 (2 ULg)
Full Text
Peer Reviewed
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 ▲]

Detailed reference viewed: 24 (2 ULg)
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)
Full Text
Peer Reviewed
See detailSomatotrope GHRH/GH/IGF-1 axis at the crossroad between immunosenescence and elder frailty
Bodart, Gwennaëlle ULg; Goffinet, Lindsay; Morrhaye, Gabriel et al

in Annals of the New York Academy of Sciences (2015), 1351

Immunosenescence as complex modifications of immunity with age could be related to the so-called frailty syndrome of elderly leading to an inadequate response to minimal aggression. Functional decline ... [more ▼]

Immunosenescence as complex modifications of immunity with age could be related to the so-called frailty syndrome of elderly leading to an inadequate response to minimal aggression. Functional decline, the loss of ability to perform activities of daily living, is related to the decrease in physiological reserves and frailty and is a frequent outcome of hospitalization in older patients. Links between immunosenescence and frailty were explored and 20 immunological parameters were affected in seniors with functional decline. IGF-1, thymopoeisis and telomere length were part of these markers. A strong relationship between insulin-like growth factor-1 (IGF-1) and thymic ouput was evidenced. IGF-1, mediator of GH, was subsequently shown to induce IL-7 secretion in cultured primary human thymic epithelial cells (TECs). We are also exploring the ‘stress hypothesis’ according which an acute stress is the discriminator revealing a frailty susceptility. GH can counteract the deleterious immunosuppressive effect of stress-induced steroids. Under non-stressing conditions, the immunosenescent system preserves physiological responses, while in stressing conditions, the combination of immunosenescence and a defect in somatotrope axis might lead to functional decline. [less ▲]

Detailed reference viewed: 69 (5 ULg)
Full Text
Peer Reviewed
See detailHow does thymus infection by coxsackievirus contribute to the pathogenesis of type 1 diabetes?
Michaux, Hélène ULg; Martens, Henri ULg; Jaïdane, Hela et al

in Frontiers in Immunology (2015), 6(Article 338), 1-6

Through synthesis and presentation of neuroendocrine self-antigens by major histocom- patibility complex proteins, thymic epithelial cells (TECs) play a crucial role in programing central immune self ... [more ▼]

Through synthesis and presentation of neuroendocrine self-antigens by major histocom- patibility complex proteins, thymic epithelial cells (TECs) play a crucial role in programing central immune self-tolerance to neuroendocrine functions. Insulin-like growth factor- 2 (IGF-2) is the dominant gene/polypeptide of the insulin family that is expressed in TECs from different animal species and humans. Igf2 transcription is defective in the thymus of diabetes-prone bio-breeding rats, and tolerance to insulin is severely decreased in Igf2−/− mice. For more than 15 years now, our group is investigating the hypothesis that, besides a pancreotropic action, infection by coxsackievirus B4 (CV- B4) could implicate the thymus as well, and interfere with the intrathymic programing of central tolerance to the insulin family and secondarily to insulin-secreting islet β cells. In this perspective, we have demonstrated that a productive infection of the thymus occurs after oral CV-B4 inoculation of mice. Moreover, our most recent data have demonstrated that CV-B4 infection of a murine medullary (m) TEC line induces a significant decrease in Igf2 expression and IGF-2 production. In these conditions, Igf1 expression was much less affected by CV-B4 infection, while Ins2 transcription was not detected in this cell line. Through the inhibition of Igf2 expression in TECs, CV-B4 infection could lead to a breakdown of central immune tolerance to the insulin family and promote an autoimmune response against insulin-secreting islet β cells. Our major research objective now is to understand the molecular mechanisms by which CV-B4 infection of TECs leads to a major decrease in Igf2 expression in these cells. [less ▲]

Detailed reference viewed: 41 (4 ULg)
See detailTreg/Th17 balance during murine embryo implantation and pregnancy
Polese, Barbara ULg; Gridelet, Virginie ULg; Araklioti, Eleni et al

Poster (2014, November)

Detailed reference viewed: 53 (12 ULg)
Full Text
Peer Reviewed
See detailThe endocrine milieu and CD4 T-lymphocyte polarization during pregnancy
Polese, Barbara ULg; Gridelet, Virginie ULg; Arakioti, Eleni et al

in Frontiers in Endocrinology (2014), 5(Article 106), 1-11

Acceptance of the fetal semi-allograft by the mother’s immune system has become the focus of intensive research. CD4+ T cells are important actors in the establishment of pregnancy. Th1/Th2 paradigm has ... [more ▼]

Acceptance of the fetal semi-allograft by the mother’s immune system has become the focus of intensive research. CD4+ T cells are important actors in the establishment of pregnancy. Th1/Th2 paradigm has been expanded to include CD4+ regulatory T (Treg) and T helper 17 (Th17) cells. Pregnancy hormones exert very significant modulatory properties on the maternal immune system. In this review, we describe mechanisms by which the endocrine milieu modulates CD4 T cell polarization during pregnancy. We first focused on Treg and Th17 cells and on their importance for pregnancy. Secondly, we review the effects of pregnancy hormones [progesterone (P4) and estradiol (E2)] on immune cells previously described, with a particular attention to human chorionic gonadotropin (hCG). The importance of Treg cells for pregnancy is evidenced. They are recruited before implantation and are essential for pregnancy maintenance. Decreased number or less efficient Treg cells are implicated in fertility disorders. As for Th17 cells, the few available studies suggest that they have a negative impact on fertility. Th17 frequency is increased in infertile patients. With the combination of its pro-effects on Th2 and Treg cells and anti-effects on Th1 and Th17 cells, P4 contributes to establishment of a favorable environment for pregnancy. E2 effects are more dependent on the context but it seems that E2 promotes Treg and Th2 cells while it inhibits Th1 cells. hCG positively influences activities of Treg and uterine natural killer cells. This embryo signal is an essential actor for the success of pregnancy, both as the endocrine factor regulating P4 secretion by the ovarian corpus luteum, but also as a paracrine agent during implantation as well as an angiogenic and immunologic mediator during the course of gestation. Luteinizing hormone (LH) immune properties begin to be studied but its positive impact on Treg cells suggests that LH could be a considerable immunomodulator in the mouse. [less ▲]

Detailed reference viewed: 31 (9 ULg)
Full Text
Peer Reviewed
See detailPréservation de la thymopïèse dans le grand âge
RICOUR, Céline ULg; de saint hubert, Marie; Martens, Henri ULg et al

Poster (2014)

Detailed reference viewed: 18 (1 ULg)
Full Text
Peer Reviewed
See detailProgramming of neuroendocrine self in the thymus and its defect in neuroendocrine autoimmunity
Geenen, Vincent ULg; Bodart, Gwennaëlle ULg; Henry, Séverine et al

in Frontiers in Neuroscience (2013), 7

During centuries after its first description by Galen, the thymus has been considered only as a vestigial endocrine organ until the discovery in 1961 by Jacques FAP Miller of its essential role in the ... [more ▼]

During centuries after its first description by Galen, the thymus has been considered only as a vestigial endocrine organ until the discovery in 1961 by Jacques FAP Miller of its essential role in the development of T (thymo-dependent) lymphocytes. A unique thymus appeared for the first time in cartilaginous fishes some 500 millions years ago, in the same time or shortly after the emergence of the adaptive (acquired) immune system. The thymus may be compared to a small brain or a computer highly specialized in the orchestration of central immunological self-tolerance. This latter was a necessity for the survival of species given the potent evolutionary pressure impacted by the high risk of autotoxicity inherent to the stochastic generation of the diversity of immune cell receptors that characterize the adaptive immune response. The new paradigm of neuroendocrine self-peptides has been proposed together with the definition of neuroendocrine self. Neuroendocrine self-peptides are not secreted by thymic epithelial cells (TECs) according to the classic model of neuroendocrine signaling, but processed for a presentation by, or in association with, the thymic major histocompatibility complex (MHC) proteins. The autoimmune regulator (AIRE) gene/protein controls the transcription of neuroendocrine genes in TECs. The presentation of self-peptides in the thymus is responsible for the clonal deletion of self-reactive T cells emerging during the random recombination of gene segments that encode variable parts of the T cell receptor for the antigen (TCR). In the same time, self-antigen presentation in the thymus also generates regulatory T (Treg) cells that are able to inhibit in the periphery self-reactive T cells having escaped negative selection in the thymus. Several arguments show that the origin of autoimmunity directed against neuroendocrine glands primarily results from a defect in the intrathymic programming of self-tolerance to neuroendocrine functions. This defect may be genetic or acquired during an enteroviral infection, for example. This novel knowledge of normal and pathologic functions of the thymus already constitutes a solid basis for the development of a novel type of tolerogenic/negative self-vaccination against type 1 diabetes (T1D). [less ▲]

Detailed reference viewed: 83 (15 ULg)
Full Text
Peer Reviewed
See detailExpression of growth hormone (GH)/insulin-like growth factor (IGF) axis during Balb/c ontogeny and effects of GH upon ex-vivo T-cell differentiation
Kermani, Hamid; Goffinet, Lindsay ULg; Mottet, Marie ULg et al

in Neuroimmunomodulation (2012), 19

Aims: We here address the question of expression and role of GH/IGF axis in the thymus. Methods: Using RT-qPCR, the expression profile of various components of the somatotrope GH/IGF axis was measured in ... [more ▼]

Aims: We here address the question of expression and role of GH/IGF axis in the thymus. Methods: Using RT-qPCR, the expression profile of various components of the somatotrope GH/IGF axis was measured in different thymic cell types and during thymus embryogenesis in Balb/c mice. Effect of GH on T-cell differentiation was explored through thymic organotypic culture. Results: Transcription of Gh, Igf1, Igf2 and their related receptors predominantly occurred in thymic epithelial cells (TEC), while a low level of Gh and Igf1r transcription was also evidenced in thymic T cells (thymocytes). Gh, Ghr, Ins2, Igf1, Igf2, and Igfr1, displayed distinct expression profiles depending on the developmental stage. The protein concentration of IGF-1 and IGF-2 were in accordance with the profile of their gene expression. In fetal thymus organ cultures (FTOC) derived from Balb/c mice, treatment with exogenous GH resulted in a significant increase of double negative CD4-CD8- T cells and CD4+ T cells, together with a decrease in double positive CD4+CD8+ T cells. These changes were inhibited by concomitant treatment with GH and GHR antagonist pegvisomant. However, GH treatment also induced a significant decrease in FTOC Gh, Ghr and Igf1 expression. Conclusion: These data show that the thymotropic properties of the somatotrope GH/IGF-1 axis involve an interaction between exogenous GH and GHR expressed by TEC. Since thymic IGF-1 is not increased by GH treatment, the effects of GH upon T-cell differentiation could implicate a different local growth factor or cytokine. [less ▲]

Detailed reference viewed: 116 (42 ULg)
Peer Reviewed
See detailInvestigations on the mechanisms underlying the thymotropic properties of the growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis.
Goffinet, Lindsay ULg; Bodart, Gwennaëlle ULg; Renard, Chantal et al

Poster (2011, November 18)

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

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

Detailed reference viewed: 100 (34 ULg)