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Horm Metab Res 2003; 35(11/12): 656-663
DOI: 10.1055/s-2004-814161
Original
© Georg Thieme Verlag Stuttgart · New York

The Thymic Insulin-like Growth Factor Axis: Involvement in Physiology and Disease

V.  Geenen1
  • 1 University of Liege Center of Immunology (CIL), Institute of Pathology, Liege-Sart Tilman, Belgium
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Publication History

Received 28 August 2003

Accepted after Revision 25 September 2003

Publication Date:
07 January 2004 (online)

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Abstract

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.

Key words

Thymus epithelium - Self-tolerance - Autoimmunity - Type 1 diabetes - T-cell leukemia - Tolerogenic vaccine

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V. Geenen M. D., Ph. D.

Research Director of Belgian NFSR and Director of CIL, Institute of Pathology CHU-B23

B-4000 Liege-Sart Tilman · Belgium

Phone: + 32 (4) 366 25 50

Fax: + 32 (4) 366 29 77 ·

Email: vgeenen@ulg.ac.be