title: TrkAIII expression in the thymus.
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.
authors.affiliation: Department of Experimental Medicine, University of L'Aquila, Coppito 2, Via Vetoio, 67100 L'Aquila, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Tacconelli
authors.forename: Antonietta R
authors.initials: AR
authors.lastname: Farina
authors.forename: Lucia
authors.initials: L
authors.lastname: Cappabianca
authors.forename: Gesilia
authors.initials: G
authors.lastname: Cea
authors.forename: Sonia
authors.initials: S
authors.lastname: Panella
authors.forename: Antonella
authors.initials: A
authors.lastname: Chioda
authors.forename: Rita
authors.initials: R
authors.lastname: Gallo
authors.forename: Benedetta
authors.initials: B
authors.lastname: Cinque
authors.forename: Roberta
authors.initials: R
authors.lastname: Sferra
authors.forename: Antonella
authors.initials: A
authors.lastname: Vetuschi
authors.forename: Antonio Francesco
authors.initials: AF
authors.lastname: Campese
authors.forename: Isabella
authors.initials: I
authors.lastname: Screpanti
authors.forename: Alberto
authors.initials: A
authors.lastname: Gulino
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Mackay
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015703:Antigens, CD / Q000378:metabolism; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D004847:Epithelial Cells / Q000502:physiology; D005434:Flow Cytometry / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D019169:Jurkat Cells; D051379:Mice; D009447:Neuroblastoma; D020917:Receptor, trkA / Q000235:genetics* / Q000378:metabolism*; D013949:Thymus Extracts / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology* / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D013949:Thymus Extracts; D020917:Receptor, trkA