Neuroendocrine control of thymus physiology

The thymus gland is a central lymphoid organ in which bone marrow-derived T cell precursors undergo differentiation, eventually leading to migration o f positively selected thymocytes to the peripheral lymphoid organs. This di fferentiation occurs along with cell migration in the context of the thymic microenvironment, formed of epithelial cells, macrophages, dendritic cells , fibroblasts, and extracellular matrix components. Various interactions oc curring between microenvironmental cells and differentiating thymocytes are under neuroendocrine control. In this review, we summarize data showing th at thymus physiology is pleiotropically influenced by hormones and neuropep tides. These molecules modulate the expression of major histocompatibility complex gene products by microenvironmental cells and the extracellular mat rix-mediated interactions, leading to enhanced thymocyte adhesion to thymic epithelial cells. Cytokine production and thymic endocrine function therei n exemplified by thymulin production) are also hormonally controlled, and, interestingly in this latter case, a bidirectional circuitry seems to exist since thymic-derived peptides also modulate hormonal production. In addition to their role in thymic cell proliferation and apoptosis, hormo nes and neuropeptides also modulate intrathymic T cell differentiation, inf luencing the generation of the T cell repertoire. Finally, neuroendocrine control of the thymus appears extremely complex, wi th possible influence of biological circuitry involving the intrathymic pro duction of a variety of hormones and neuropeptides and the expression of th eir respective receptors by thymic cells.