The thymic insulin-like growth factor axis: involvement in physiology and disease.
A repertoire of neuroendocrine-related genes is transcribed in the non-lymphoid compartment of the thymus, transposing the dual physiological role of this organ at the molecular level in T-cell development towards the establishment of central T-cell self-tolerance. The "neuroendocrine self" has been defined as a series of antigen sequences processed from precursors predominantly expressed in the thymus and first encountered by differentiating T-lymphocytes in their early life. All the members of the insulin gene family are expressed in the thymus according to a precise hierarchy and cellular topography, whereby IGF-II (epithelium of the subcapsular cortex and medulla) exceeds IGF-I (macrophages), which in turn far exceeds INS (rare subsets of medullary epithelial cells). This hierarchy in the degree of their respective thymic expression explains why IGF-II is more tolerated than IGF-I, and much more so than insulin. Evidence has been found for significant regulatory/tolerogenic properties in the IGF-II B:11 - 25 sequence after analysis of the cytokine secretion profile in peripheral blood mononuclear cells isolated from ten DQ8+ type 1 diabetic adolescents. In the thymus, IGF ligands and receptors also intervene in the control of T-cell proliferation and differentiation. Here, we also discuss how a disturbance in the intrathymic IGF-mediated signaling could contribute to the pathogenesis of T-cell leukemia.
Geenen
V
V
University of Liege Center of Immunology, Institute of Pathology, Liege-Sart Tilman, Belgium. vgeenen@ulg.ac.be
D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000517:prevention & control; D006801:Humans; D007108:Immune Tolerance; D007328:Insulin / Q000276:immunology; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D007335:Insulin-Like Growth Factor II / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology / Q000502:physiology* / Q000503:physiopathology
D007328:Insulin; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II