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Muriel MOSER


coordonnées


UR en Immunobiologie
Muriel MOSER
tel 02 650 98 63, fax 02 650 98 60, Muriel.Moser@ulb.ac.be
Campus de Charleroi
CP300, rue des Professeurs Jeener et Brachet 12, 6041 Charleroi (Gosselies)



unités de recherche


Immunobiologie (anciennement Physiologie animale) [Immunobiology (formerly Animal Physiology)]



projets


Développement et fonction des cellules ''T helper'' dans la production d'anticorps in vivo [Development and function of helper T cells for antibody production in vivo]
voir version anglaise [Humoral immune protection against pathogens relies on the development of high affinity antibodies produced by activated B cells that differentiated further in memory B cells or long-lived plasma cells. This process takes place in the germinal centers and depends on a subset of CD4+ T cells called T follicular helper (Tfh). Although many studies are devoted to this novel T helper cell population, the molecular mechanisms governing Tfh cell differentiation have yet to be characterized and better understanding of this crucial immune process would have major implications in immune disease treatment and vaccine formulation. In particular modulating Tfh cell activation in vivo may help to develop long term humoral responses that lack allergic, IgE-mediated side effects. Our research group has demonstrated IL-6 promotes the differentiation of naïve T cells into follicular helper T cells. IL-6 appears to control Tfh differentiation in a STAT3 dependent fashion, suggesting an important role for this transcription factor in the control of humoral responses. STAT3 activation also allowed the conversion of Th2 cells into Tfh cells, suggesting that some 'plasticity' exist between T helper cells and highlighting a possible role for the IL-6 / STAT3 signaling pathway in the conversion of pathogenic allergic (IgE) Th2 responses into protective (IgG) humoral Tfh responses.Our current research objective is to identify the molecular mechanism by which STAT3 controls T cells differentiation. In particular, our project aims at understanding the functional relationship between STAT3 and other transcription factors (such as BCL6 and cMAF) known to play a role in T follicular helper differentiation and function. Finally, based on recent finding indicating a role for cell metabolism in the control of T cell differentiation, we plan to explore the possible relationship between intracellular levels of important metabolites (such as NAD and ATP) and STAT3 activation. This novel avenue of research may shed light on a possible link between the nutritional status and the development of humoral immune responses, a finding of potential clinical relevance in the field of vaccination. ]

NAD Métabolisme cellulaire et régulation des réponses immunes [NAD metabolism and regulation of immune responses ]
voir version anglaise [During a study aiming at the identification of genes selectively expressed by immune cells, our laboratory has identified over a decade ago the gene coding for a nicotinamidephosphoribosyltransferase (Nampt), an enzyme involved in NAD biosynthesis. Of interest, expression of this gene was found upregulated following antigen stimulation of both innate and adaptive cells. These observations, independently confirmed by others, led us to further explore the possible relationship between NAD metabolism and the control of immune responses. Nicotinamide adenine dinucleotide (NAD) has been known for several decades to play a major role as a coenzyme in numerous oxidation-reduction reactions. Recently however, the distinct role of NAD as a precursor for molecules involved in regulatory processes has also been recognized. Numerous enzymesinvolved in post-translational modification of target proteins and using NAD as a substrate have been identified in mammals and include mono and poly (ADP-ribosyl) transferases (respectively mARTs and PARPs) and deacylases such as Sirtuins. This later family comprises seven members (SIRT1 to SIRT7), whosedeacylase activity appears as strictly linked to intracellular NAD levels. Though the modulation of intracellular NAD levels, Nampt appears therefore to play an important role in the regulation of sirtuin activity. Notably, sirtuins have recently attracted great interest following the demonstration that they may play a role in cell longevity and responses to stress. Based on these considerations, we have undertaken a series of research projects to evaluate the role of the Nampt-NAD-sirtuin axis in the regulation of an immune response. These studies have led to the discovery of the important role of Nampt in lymphocyte development and in the control of TNF (an important pro-inflammatory factor) secretion. Our current studies aim at identifying the role of sirtuins in other aspects of immune regulation including T lymphocyte activation and differentiation. ]



disciplines et mots clés déclarés


Immunologie

anticorps centres germinatifs immunologie inflammation régulation sirtuine tfh