Expression of Preprotachykinin-A and Neuropeptide-Y Messenger RNA in the Thymus

Abstract

The preprotachykinin-A gene, the common gene of mRNAs encoding both substance-P (SP) and neurokinin-A (NKA), was shown to be expressed in Sprague-Dawley rat thymus by detection of specific mRNA in gel-blot analyses. In situ hybridization revealed dispersed PPT-A-labeled cells in sections from rat thymus, with a concentration of grains over a subpopulation of cells in the thymic medulla. Also, neuropeptide-Y mRNA-expressing cells were found in the rat thymus, primarily in the thymic medulla. Rat thymic extracts contained SP-like immunoreactivity (SP-LI), and the major part of the immunoreactivity coeluted with authentic SP and SP sulfoxide standards. SP-LI was also detected in human thymus, which contained between 0.09-0.88 ng SP-LI/g wet wt. Evidence for translation of preprotachykinin-A mRNA in the rat thymus was obtained from the demonstration of NKA-LI in thymic cells with an epithelial-like cell morphology. Combined with previous observations on the immunoregulatory roles of tachykinin peptides and the existence of specific receptors on immunocompetent cells, the demonstration of intrathymic synthesis of NKA suggests a role for NKA-LI peptides in T-cell differentiation in the thymus.

Cytokine production by human thymic epithelial cells: control by the immune recognition of the neurohypophysial self-antigen

“…Somehow like the transduction following the binding of a signal to its receptor, the immunological recognition of OT leads to TEC activation reflected here by the secretion of IL-6 and LIF. It will be also of interest to determine whether Abs against other thymic self-antigens such as neurokinin A [39] and insulin-like growth factor II [40,41] are also able to affect TEC secretory activity. At the present stage, this study supports our model on the dual physiological role played in T-cell differentiation by the thymic repertoire of neuroendocrine-related polypeptides [8,9].…”

Les cibles hormonales de la réponse auto-immune

“…Toutefois, nos travaux ont démontré que les cellules épithéliales thymiques (CET) sont le siège de la transcription d'un grand nombre de gènes appartenant à plusieurs familles neuroendocrines, comme celles des hormones neurohypophysaires [9], des tachykinines [10], de la neurotensine [11] et de l'insuline [12]. La nature du « soi neuroendocrine » a été ensuite définie comme suit :…”

“…La liaison de l'ocytocine à son récepteur exprimé par les cellules T thymiques provoque une phosphorylation rapide des kinases liées à l'adhésion focale [13], qui pourrait jouer un rôle dans la promotion de synapses immunologiques entre les cellules thymiques présentatrices d'antigènes (CPA), comme les CET et les cellules T immatures. La neurokinine A -et non la substance P -est le peptide généré par l'apprêtement dans les CET du produit d'expression du gène de la préprotachykinine A [10]. En ce qui concerne la famille de l'insuline, l'expression thymique du facteur de croissance apparenté à l'insuline de type 2 (IGF-2) prédomine pendant la vie foetale sur celle de l'IGF-1, elle-même étant supérieure à celle de l'insuline (12 ; Hansenne et al, soumis pour publication).…”

Ontogenesis and functional aspects of oxytocin and vasopressin gene expression in the thymus network

“…The repertoire of thymic neuroendocrine precursors expressed is organized in such a way that one dominant member per family is expressed in the thymus. Thymic neuroendocrine selfantigens usually correspond to sequences highly conserved throughout evolution of one given family: oxytocin (OT) vs. vasopressin (VP) for the family of related hormones, neurokinin A vs. substance P for tachykinins (Ericsson et al, 1990), and insulin-like growth factor 2 (IGF-2) vs. IGF-1 and proinsulin for the insulin family (Geenen et al, 1993;Martens et al, 1996a).…”