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Anaelle TAQUIN


UR en Immunobiologie
Anaëlle TAQUIN
Campus de Charleroi - Gosselies (Biopark)
CP300, rue des Professeurs Jeener et Brachet 12, 6041 Charleroi (Gosselies)

unités de recherche

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


Réponse immunitaire innée dans l'infection et cancer (débuté en 2014) [The innate immune response in infection and cancer (starting in 2014)]
voir version anglaise [The innate immune response is the first line of defense against infections. The innate immune system recognizes pathogens and contributes to their elimination by a diversity of mechanisms. However, an excessive or dysregulated innate response can result in tissue damage and cause pathology. Therefore, a delicate balance needs to be established between the activation and regulation of the immune response in the context of infection.The innate immune system also plays critical roles in cancer initiation, development and metastasis. Depending on the tumor microenvironment, the immune system can either contribute to the elimination of the tumor, or support tumor growth. The molecular mechanisms that determine the anti-tumoralvs. tumor-supporting properties of the immune system are still poorly understood.We use two complementary approaches to address these questions:1) We use mouse models, which can be easily manipulated genetically and experimentally in the laboratory, in order to understand the general principles that govern the mammalian innate immune responsein vivo.2) Mice and humans are separated by ~180 million years of divergent evolution. As a consequence,major differences exist between the immune systems of these two species and frequently, knowledge gained from animal studies cannot be directly translated in the human species. Furthermore, obvious practical and ethical barriers restrict experimentation on human subjects in vivo. To circumvent these limitations, we developed novel models of mice repopulated with a functional human immune system (so-called 'humanized mice'), which combine the advantage of a small animal model with the specificities of the human species. Our work consists in (a) developing and characterizing improved models of humanized mice; and (b) using these models to understand the cellular and molecular mechanisms of the human immune response to infection and cancer in vivo.]

Immunité intestinale [Intestinal Immunity]
voir version anglaise [In microenvironments such as the gastrointestinal tract, in which immune reactivity against intestinal flora or dietary antigen poses a significant risk to the host, immunosuppressive, regulatory elements predominate to suppress local inflammation. Nevertheless, even in highly regulated sites, immune responses need to occur to allow proper control of microbial expansion. How mucosal immune responses inside this tolerance-prone environment are regulated remains largely elusive.ATP is one of the universal cell energy metabolite and functions also as extracellular signaling molecules. In the immune system, extracellular ATP works as a 'danger' signal. The ATP sources are multiple: in particular, cell damage leads to a marked increase in the ATP concentration in the immediate extracellular milieu and intestinal bacteria are able to generate and secrete large amounts of ATP. These observations suggest that, inside the intestine, where T cells are chronically activated and in close contact with intestinal flora, the extracellular ATP generation needs to be tightly regulated to avoid excessive immune activation leading eventually to immunopathology.There is evidence that intestinal T cells are able to mediate extracellular ATP catabolism via the expression of two ectonucleotidase: CD39 and CD73. This capacity to remove ATP from the extracellular space and to generate adenosine seems to negatively regulate the intestinal immune response.Ourfirst objective is therefore to study the role of adenosine in the regulation of mucosal immune responses, including the differentiation and effector function of helper T cells and regulatory T cells.Secondly, inflamed tissue can become hypoxic. T cells are able to sense hypoxia by the Hypoxia inducible transcription factor (HIF-1), a heterodimeric protein composed of two subunits: HIF-1α and HIF-1β.Our second objective is to test whether specialized T helper subsets are differentially adapted to hypoxia and how these inflammatory effector cells can operate in a hypoxic tissue. Understanding the immunomodulatory role of adenosine and the mechanisms underlying immune cell adaptation to hypoxia would help to identify the cellular and molecular pathways involved in immunoregulation in normal, inflamed or cancerous tissues.]

Immunothérapie du cancer [Cancer immunotherapy]
voir version anglaise [There is increasing evidence that the effect of chemotherapy on tumor growth is not cell autonomous but relies on the immune system. The objective of our study is to better understand how the host immune system is involved in the success of chemotherapy. We use the P815 mastocytoma of DBA/2 mice, as this tumor is poorly immunogenic, expresses well defined antigens and can elicit the differentiation of T cells specific to tumor-associated and/or tumor-specific antigens in some conditions. We have shown recently that treatment of DBA/2 mice bearing P815 mastocytoma with cyclophosphamide induced rejection and long-term protection in a CD4- and CD8-dependent manner. A population of inflammatory-type dendritic cells was dramatically expanded in the lymph nodes of mice that rejected the tumor and correlated with CD4-dependent infiltration, in tumor bed, of tumor-specific CD8+ T lymphocytes. Our data point to a major role of CD4+ T cells in inducing chemokine expression in the tumor, provoking migration of tumor-specific CXCR3+ CD8+ T lymphocytes.Importantly, the analysis of CD8+ T cells specific to P1A/H-2Ld and P1E/H-2Kd revealed that cyclophosphamide altered the P815-specific CD8 T repertoire by amplifying the response specific to the mutated P1E antigen. This question is of major importance for immunotherapy to define the role of tumor-associated (encoded by cancer-germline gene) versus tumor-specific (encoded by a mutated gene) antigens as tumor rejection antigens.Collectively our observation reinforce the concept that chemotherapy relies on the immune response to achieve full remission in an experimental tumor model and suggest that that in some instances, chemotherapy may achieve long term effects by favoring the establishment of an immune, memory-like anti-tumor response. Future experiments will attempts to better understand the mechanism whereby chemotherapeutic agents such as cyclophosphamide allow the establishment of an effective immune response to tumor antigens. ]

disciplines et mots clés déclarés

Biologie cellulaire Immunologie

atp cancer flore intestinale hif immunothérapie intestin réponse innée souris humanisées