TrkAIII expression in the thymus

• Published in: Journal of neuroimmunology Vol. 183; no. 1; pp. 151 - 161
• Main Authors: Tacconelli, Antonella, Farina, Antonietta R, Cappabianca, Lucia, Cea, Gesilia, Panella, Sonia, Chioda, Antonella, Gallo, Rita, Cinque, Benedetta, Sferra, Roberta, Vetuschi, Antonella, Campese, Antonio Francesco, Screpanti, Isabella, Gulino, Alberto, Mackay, Andrew R
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-02-2007
• Subjects: Allergy and Immunology; Alternative TrkAIII splicing; Animals; Animals, Newborn; Antigens, CD - metabolism; Cells, Cultured; Embryo, Mammalian; Epithelial Cells - physiology; Flow Cytometry - methods; Gene Expression Regulation, Neoplastic; Humans; Hypoxia; Immunohistochemistry - methods; Jurkat Cells; Mice; Neuroblastoma; Neurology; Receptor, trkA - genetics; Receptor, trkA - metabolism; Thymic epithelial cells; Thymocytes; Thymus; Thymus Extracts - metabolism; Thymus Gland - cytology; Thymus Gland - metabolism; Hypoxia; Thymocytes; Thymic epithelial cells; Alternative TrkAIII splicing; Thymus
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/j.jneuroim.2006.12.005

Abstract The alternative TrkAIII splice variant is expressed by murine and human thymus. Alternative TrkAIII splicing predominates in postembryonic day E13 (E17 and E18), postnatal murine (3 week and 3 month) and human thymuses, with TrkAIII mRNA expressed by selected thymocyte subsets and thymic epithelial cells (TECs) and a 100 kDa immunoprecipitable TrkAIII-like protein detected in purified thymocyte and whole thymus extracts. FACS and immunohistochemical analysis indicate a non-cell surface localisation for the TrkAIII-like protein in cortical CD4+ /CD8+ double positive and, to a lesser extent, single positive thymocyte subsets at the cortex/medulla boundary and in Hassle's corpuscles, reticular epithelial and dendritic cells of the thymic medulla. TrkA(I/II) expression, on the other hand, predominates in sub-capsular regions of the thymus. TrkAIII-like immunoreactivity at the cortex/medulla boundary associates with regions of thymocyte proliferation and not apoptosis. A potential role for thymic hypoxia in thymocyte alternative TrkAIII splicing is supported by reversal to TrkAI splicing by normoxic but not hypoxic culture and induction of Jurkat T cell alternative TrkAIII splicing by the hypoxia mimic CoCl2 . In contrast, TEC expression of TrkAIII predominates in both normoxic and hypoxic culture conditions. The data support a potential role for TrkAIII in thymic development and function, of particular relevance to intermediate stage CD4+ /CD8+ thymocyte subsets and TECs, which potentially reflects a reversible thymocyte and more permanent TEC adaptation to thymic environment. Since intracellular TrkAIII neither binds nor responds to NGF and can impede regular NGF/TrkA signalling (Tacconelli et al., Cancer Cell, 2004), its expression would be expected to provide an alternative and/or impediment to regular NGF/TrkA signalling within the developing and developed thymus of potential functional importance.