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Unravelling human T cell development in health and disease

 

T cells are a crucial part of the human adaptive immune system and its development is often perturbed in immunodeficiencies and T cell leukemias. By understanding the transcriptional network that induces and controls human T cell development in both a normal and malignant setting, our work might help in obtaining novel insights in key mechanisms driving T cell development in a fundamental and clinical context.

 

 

Multipotent hematopoietic stem cells (HSCs), which are formed in the bone marrow during the early stages of life, are capable of generating the broad repertoire of human blood cells. These HSCs migrate to the micro-environment of the thymus where different stimuli direct these progenitors to form the T lymphocytes. Here, these precursors undergo a step-wise conversion towards mature T lymphocytes that is driven by an interplay of key factors such as Notch signalling. Finally, these fully differentiated T cells migrate to the periphery where they become an essential part of the adaptive immune system.

In a more clinical context, the HSCs are transplanted to rebuild the immune system after chemotherapy. The downside of these transplants is the slow and poor reconstitution of T lymphocytes, leading to a prolonged window of immunodeficiency in which patients are highly susceptible to opportunistic infections. By unravelling the molecular network that controls the differentiation of HSCs into T cells, our work might help to improve the generation of T cells following HSC transplantation. In addition, since many of the key transcription regulators that drive the development of mature T cells are often aberrantly expressed during T cell leukemia, another part of our work aims to reveal how these factors drive oncogenic transformation during T cell differentiation. In this way, by studying the malignant alterations that occur, these fundamental insights might provide novel opportunities for targeted therapy.

The Taghon lab is a young and dynamic research group founded by emeritus prof. dr. Jean Plum. Focusing on human T cell development, the team attempts to unravel the molecular signature that drives T cell development using state-of the art techniques, equipment and know-how. In a malignant context, the Taghon Lab closely collaborates with the lab of prof. dr. Pieter Van Vlierberghe, who is an expert in the field of malignant transformations that occur during the development of T cell leukemia.

 

 

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