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See detailImpact of the somatotrope Growth Hormone (GH)/Insulin-like Growth Factor 1 (IGF-1) axis upon thymus function: Pharmacological implications in regeneration of immune functions
Goffinet, Lindsay ULg; Mottet, Marie ULg; Kermani, Hamid et al

in Immunology, Endocrine & Metabolic Agents - Medicinal Chemistry (2011), 11

The thymus is the central lymphoid structure where T-cell differentiation takes place, and a crucial organ for the maintenance of homeostasis in the immune system. Thymopoiesis includes intrathymic ... [more ▼]

The thymus is the central lymphoid structure where T-cell differentiation takes place, and a crucial organ for the maintenance of homeostasis in the immune system. Thymopoiesis includes intrathymic proliferation of T-cell precursors, selection and output of both self-tolerant and competent effector T cells, as well as of natural regulatory T cells (nTreg). In the crosstalk between the neuroendocrine and immune systems, peptide hormones have been more and more implicated in immunomodulation for the last thirty years. The somatotrope growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis in particular has been repeatedly shown to play a major regulatory role upon thymus function and T-cell development. This review will focus on the important thymotropic properties of the somatotrope GH/IGF-1 axis, and will try to discriminate these properties in function of the endocrine or paracrine/autocrine pathways involved in their mediation. Most importantly, in light of an increasing number of recent studies, GH and IGF-1 now appear as a novel therapeutic agents that could be used for enhancing thymopoiesis in different cases of immune deficiencies, including aging-related immune dysfunction. [less ▲]

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See detailTranscriptomic biomarkers of the response of hospitalized geriatric patients admitted with heart failure. Comparison to hospitalized geriatric patients with infectious diseases or hip fracture
Vo, Thi Kim Duy; de Saint-Hubert, Marie; Morrhaye, Gabriel et al

in Mechanisms of Ageing & Development (2011), 132

The abundance of a preselection of transcripts involved in inflammation, immunosenescence and stress response was compared between PBMC of healthy aged donors and aged patients in acute phase of heart ... [more ▼]

The abundance of a preselection of transcripts involved in inflammation, immunosenescence and stress response was compared between PBMC of healthy aged donors and aged patients in acute phase of heart failure and at recovery. This study identified 22 transcripts differentially abundant in acute phase of heart failure versus healthy aged subjects. Transcripts involved in inflammation and oxidative stress weremore abundant. Those associated with T-cell functions were less abundant. The results were compared to two other major acute geriatric issues: infectious diseases and hip fracture. In acute phase, compared to healthy aged subjects, the abundance of 15/22 transcripts was also altered in both geriatric infectious diseases and hip fracture. Many variations had not vanished at the recovery phase. The abundance of CD28, CD69, LCK, HMOX1, TNFRSF1A transcripts, known to be altered in healthy aged versus healthy young subjects, was further affected in acute phase of the three geriatric diseases considered. The transcript levels of BCL2, CASP8, CCL5, DDIT3, EGR3, IL10RB, IL1R2, SERPINB2 and TIMP1 were affected in all three pathological conditions compared to healthy aged, but not versus healthy young subjects. In conclusion, this work provides critical targets for therapeutic research on geriatric heart failure, infectious diseases and hip fracture. [less ▲]

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See detailDifferentially abundant transcripts in PBMC of hospitalized geriatric patients with hip fracture compared to healthy aged controls
Vo, Thi Kim Duy; Godard, Patrice; de Saint-Hubert, Marie et al

in Experimental Gerontology (2011), 46

The abundance of a selection of transcript species involved in in!ammation, immunosenescence and stress response was compared between PBMC of 35 geriatric patients with hip fracture in acute phase (days ... [more ▼]

The abundance of a selection of transcript species involved in in!ammation, immunosenescence and stress response was compared between PBMC of 35 geriatric patients with hip fracture in acute phase (days 2–4 after hospitalization) or convalescence phase (days 7–10) and 28 healthy aged controls. Twenty-nine differentially abundant transcripts were identi"ed in acute phase versus healthy ageing. Twelve of these transcripts remained differentially abundant in convalescence phase, and 22 were similarly differentially abundant in acute phase of geriatric infectious diseases. Seven of these 22 transcripts were previously identi"ed as differentially abundant in PBMC of healthy aged versus healthy young controls, with further alteration for CD28, CD69, LCK, CTSD, HMOX1, and TNFRSF1A in acute phase after geriatric hip fracture and infectious diseases. The next question is whether these alterations are common to other geriatric diseases and/or preexist before the clinical onset of the diseases. [less ▲]

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See detailImmunological principles relevant for immune-mediated inflammatory diseases and pregnancy
Geenen, Vincent ULg

Scientific conference (2010, November 23)

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See detailTranscriptomic biomarkers of human ageing in peripheral blood mononuclear cell total RNA
Duy Vo, Thy Kim; Godard, Patrice; de Saint-Hubert, Marie et al

in Experimental Gerontology (2010), 45

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See detailThymic self-antigens for the design of a negative/tolerogenic self-vaccination against type 1 diabetes.
Geenen, Vincent ULg; Mottet, Marie ULg; Dardenne, Olivier ULg et al

in Current Opinion in Pharmacology (2010), 10

Before being able to react against infectious non-self antigens, the immune system has to be educated in the recognition and tolerance of neuroendocrine proteins and this critical process takes place only ... [more ▼]

Before being able to react against infectious non-self antigens, the immune system has to be educated in the recognition and tolerance of neuroendocrine proteins and this critical process takes place only in the thymus. The development of the autoimmune diabetogenic response results from a thymus dysfunction in programming central self-tolerance to pancreatic insulin-secreting islet β cells, leading to the breakdown of immune homeostasis with an enrichment of islet β-cell reactive effector T cells and a deficiency of β-cell specific natural regulatory T cells (nTregs) in the peripheral T-lymphocyte repertoire. Insulin-like growth factor 2 (IGF-2) is the dominant member of the insulin family expressed during fetal life by the thymic epithelium under the control of the autoimmune regulator (AIRE) gene/protein. The very low degree of insulin gene transcription in normal murine and human thymus explains why the insulin protein is poorly tolerogenic as evidenced in many studies, including the failure of all clinical trials that have attempted immune tolerance to islet β cells via various methods of insulin administration. Based on the close homology and cross-tolerance between insulin, the primary T1D autoantigen, and IGF-2, the dominant self-antigen of the insulin family, a novel type of vaccination, so-called “negative/tolerogenic self-vaccination”, is currently being developed for prevention and cure of T1D. If this approach were found to be effective for reprogramming immunological tolerance in T1D, it could pave the way for the design of other self-vaccines against autoimmune endocrine diseases, as well as other organ-specific autoimmune diseases. [less ▲]

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See detailLe tabac et ses effets sur le système endocrinien
VALDES SOCIN, Hernan Gonzalo ULg; VROONEN, Laurent ULg; Latta, A. et al

in Revue Médicale de Liège (2010), 65(9), 498-501

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See detailTranscriptomic biomarkers of the response of hospitalized geriatric patients with infectious diseases
Duy Vo, Thi Kim; Godard, Patrice; de Saint-Hubert, Marie et al

in Immunity & Ageing : I & A (2010), 17

Background: Infectious diseases are significant causes of morbidity and mortality among elderly populations. However, the relationship between oxidative stress, immune function and inflammatory response ... [more ▼]

Background: Infectious diseases are significant causes of morbidity and mortality among elderly populations. However, the relationship between oxidative stress, immune function and inflammatory response in acute phase of the infectious disease is poorly understood. Results: Herein the abundance of a selection of 148 transcripts involved in immunosenescence and stress response was compared in total RNA of PBMC of 28 healthy aged probands and 39 aged patients in acute phase of infectious disease (day 2-4 after hospitalization) or in convalescence phase (day 7-10). This study provides a list of 24 differentially abundant transcript species in the acute phase versus healthy aged. For instance, transcripts associated with inflammatory and anti-inflammatory reactions (TNFRSF1A, IL1R1, IL1R2, IL10RB) and with oxidative stress (HMOX1, GPX1, SOD2, PRDX6) were more abundant while those associated with T-cell functions (CD28, CD69, LCK) were less abundant in acute phase. The abundance of seven of these transcripts (CD28, CD69, LCK, CTSD, HMOX1, TNFRSF1A and PRDX6) was already known to be altered in healthy aged probands compared to healthy young ones and was further affected in aged patients in acute phase, compromising an efficient response. Conclusion: This work provides insights of the state of acute phase response to infections in elderly patients and could explain further the lack of appropriate response in the elderly compared to younger persons. [less ▲]

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See detailHuman Chorionic Gonadotropin: a hormone with immunological and angiogenic properties.
Tsampalas, M.; Gridelet, Virginie ULg; Berndt, Sarah ULg et al

in Journal of Reproductive Immunology (2010), 85(1), 93-8

The success of implantation depends on a receptive endometrium, a normal blastocyst and synchronized cross-talk at the maternal–fetal interface. The progression of pregnancy then requires immunological ... [more ▼]

The success of implantation depends on a receptive endometrium, a normal blastocyst and synchronized cross-talk at the maternal–fetal interface. The progression of pregnancy then requires immunological tolerance which allows conceptus survival. A cascade of cytokines mediates this dialogue and is crucial in the cross-talk between the immune and endocrine systems. The first known human embryo-derived signal is chorionic gonadotropin (hCG) by which the embryo profoundly influences immunological tolerance and angiogenesis at the maternal–fetal interface. hCG levels coincide with the development of trophoblast tolerance. Indeed, it increases the number of uterine natural killer cells that play a key role in the establishment of pregnancy. hCG also intervenes in the development of local immune tolerance through the cellular system of apoptosis via Fas/Fas-Ligand. It modulates the Th1/Th2 balance and acts on complement C3 and C4A/B factors modulating decidual immunity. The transient tolerance evident during gestation is at least partially achieved via the presence of regulatory T cells which are attracted by hCG at the fetal–maternal interface. Finally, hCG treatment of activated dendritic cells results in an up-regulation of MHC class II, IL-10 and IDO expression, reducing the ability to stimulate T cell proliferation. Successful implantation requires an extensive endometrial angiogenesis in the implantation site. Recent data demonstrate angiogenic effects of hCG via its interaction with endometrial and endothelial LH/hCG receptors. Our review focuses on these functions of hCG, giving new insight into the endocrine–immune dialogue that exists between the conceptus and immune cells within the receptive endometrium at the time of implantation. [less ▲]

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See detailCurrent Opinion in Pharmacology, Volume 10, Issue 4, Section Immunomodulation
Geenen, Vincent ULg

in Current Opinion in Pharmacology (2010), 10(Issue 4), 405-504

Detailed reference viewed: 50 (6 ULg)