Thymus oxytocin, self-tolerance and autoimmunity
Vincent Geenen MD, PhD (born in 1958) is Research director at the Fund of Scientific Research (FRS) of Belgium, professor of history of biomedical research and embryology at the University of Liège, and head of clinics in endocrinology at the University Hospital of Liège.
The initial intuition guiding his work was to think that the thymus as a central organ should be an essential crossroad between the nervous, endocrine and immune systems. He showed that the neurohypophysial hormone oxytocin is synthesized in thymic epithelial cells and that functional oxytocin receptors are expressed by immature T cells (thymocytes).
Focal adhesion kinases are phosphorylated after binding of oxytocin to its cognate receptors on thymocytes and this could stimulate the formation of immune synapses between thymic epithelial cells and immature T cells. With his research group, Vincent Geenen also showed that each neuroendocrine gene/protein family is represented by a dominant member expressed in thymic epithelium.
However, the most significant discovery of Geenen’s laboratory was to evidence that, in the thymus, neuropeptides are not secreted as classical (neuro)hormones but do behave as neuroendocrine self-antigens that are presented by major histocompatibility complex (MHC) proteins expressed by thymic epithelial cells. Neuroendocrine self-antigen presentation by MHC in the thymus indicated that the thymus is the sole lymphoid organ responsible for programming immune self-tolerance of neuroendocrine functions.
The same team also showed that thymus dysfunction is the primary event in the development of the autoimmune diabetogenic process. Geenen’s laboratory currently works on the development of a novel type of vaccine, a self-vaccine against autoimmune type 1 diabetes, based on the tolerogenic properties of the thymus.
Relevant references:
Immunoendocrinology in Health and Disease, Geenen V and Chrousos GP (eds.), Marcel Dekker-NY, 2004, 2007
Neuroimmunomodulation in Health and Disease, Annals of New York Academy of Sciences 1351, pp. 1-154, 2015; Edited by Geenen V
The thymus and the science of self, Geenen V, Springer Seminars in Immunopathology 43: 1-10, 2021.
Cryptocrine signaling in the thymus network and the central self-tolerance of neuroendocrine principles, Geenen V (1995), Professorial thesis, University of Liège, Belgium.
The thymic repertoire of neuroendocrine self-antigens: physiological implications in T-cell life and death, Martens H, Goxe B and Geenen V (1996), Immunology Today 17: 312-317.
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