Cryptocrine signaling in the thymus network and T cell education to neuroendocrine self-antigens

Geenen, Vincent; Goxe, Béatrice; Martens, Henri; Vandersmissen, Eric; Vanneste, Yves; Achour, Imane; Kecha, Ouafae; Lefèbvre, Pierre

doi:10.1007/bf00202263

Cited by 10 publications

(5 citation statements)

References 41 publications

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“…Insulin is of particular interest because of its restricted expression; however, its presence and that of the other pancreatic hormones in the thymus raises the question of how many peripheral proteins might be expressed there. We and others have found a wide variety of autoantigens involved in IDDM and other autoimmune diseases expressed in the thymus [11,21,45,47,48], many of which probably have functional roles. However, some like insulin may only be present to induce immune tolerance.…”

Section: Resultsmentioning

confidence: 99%

Thymic Expression of the Pancreatic Endocrine Hormones

Throsby

Pleau²,

Dardenne³

et al. 1999

Neuroimmunomodulation

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The thymus plays a central role in the selection of T lymphocytes that are tolerant to ‘self’ antigens and responsive to foreign pathogens. We and others have reported the expression of the pancreatic endocrine hormones, preproinsulin, proglucagon, prosomatostatin and propancreatic polypeptide in the human and mouse thymus. While mRNA expression is very low there is evidence for the presence of the translated product. In addition, we have investigated the cell types responsible for expression. In the thymus, hormone expression is enriched in the antigen-presenting cell population. Interestingly, while proglucagon, prosomatostatin and propancreatic polypeptide appear to be expressed in a macrophage population, preproinsulin expression was restricted to dendritic cells which are more potent antigen-presenting cells. The functional significance of the endogenous expression of insulin in the thymus has been indirectly investigated using transgenic models in which the transgene is introduced by the rat insulin promoter. The data suggest that thymic expression of the transgene is critical in the induction of T-cell tolerance to the transgene in the periphery. Taken together, the evidence suggests that the low-level pancreatic hormone expression in the thymus may be involved in central tolerance to proteins of restricted expression.

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Section: Resultsmentioning

confidence: 99%

Thymic Expression of the Pancreatic Endocrine Hormones

Throsby

Pleau²,

Dardenne³

et al. 1999

Neuroimmunomodulation

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“…Relatively little has been reported on AVP in the human immune system. AVP is found in rat and human thymic epithelial cells (7, 8, 34, 35) and in B lymphocytes in the rat spleen (36) where its expression increases in adjuvant arthritis (11). AVP has recently been reported in human PBMC (37), and AVP receptors are located on human PBMC (38).…”

Section: Discussionmentioning

confidence: 99%

Corticotropin‐Releasing Hormone Immunoreactivity in Human T and B Cells and Macrophages: Colocalization With Arginine Vasopressin

Baker

Richards

Dayan

et al. 2003

J Neuroendocrinology

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Corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) are expressed in cells of the immune system where they exert immunomodulatory roles, but these neuropeptides are poorly characterized in human immune tissues. The aim of this study was to determine concentrations and distribution of CRH and AVP in nonactivated human peripheral blood mononuclear cells (PBMC). PBMC from normal human subjects were separated into enriched subpopulations of T and B cells and monocytes/macrophages by a magnetic bead/monoclonal antibody technique. CRH and AVP were measured in cell extracts by radioimmunoassay (RIA). CRH-immunoreactivity (ir) ranged 0.24-0.8 fmol/million cells (n = 6 subjects) in T cell extracts, 0.4-2.7 fmol/million cells (n = 4) in B cells and 0.63-2.16 fmol/million cells (n = 4) in macrophages. AVP-ir ranged 0.2-0.95 fmol/million cells in T cell extracts, <0.1-0.8 fmol/million cells in B cells and 0.14-3.19 fmol/million cells in macrophages. Reversed-phase high-performance liquid chromatography (HPLC) of T and B cell extracts revealed a peak of CRH-ir which coeluted with synthetic CRH-41; this peak was not present in macrophages. A second peak of CRH-ir which eluted in a more hydrophobic position was observed in extracts of T and B cells and macrophages. This unidentified form of CRH-ir is the predominant form of CRH-ir in nonactivated human PBMC. This is the first study to demonstrate that CRH-ir and AVP-ir are colocalized within human T cells, B cells and monocytes/macrophages. We have confirmed observations of a variant form of CRH-ir in human PBMC and show that this is the predominant form in macrophages and B cells whereas CRH-ir, which coelutes with CRH(1-41) on HPLC, is present in significant amounts only in T cells. These data also confirm that CRH-ir in human PBMC is not urocortin because the antiserum used in the CRH RIA does not bind to urocortin.

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“…Our understanding of thymic physiology highly progressed with the demonstration that thymic stromal cells transcribe a repertoire of neuroendocrine-related and other peripheral tissue antigen-encoding genes (Geenen et al, 1995;Kyewski et al, 2002). Thymic neuroendocrine precursors play a dual role in T-cell selection according to their processing either as self-antigens for T-cell negative selection, or as accessory ligands for the development of self-tolerant T cells (Martens et al, 1996a).…”

Section: Introductionmentioning

confidence: 99%

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

Hansenne¹,

Rasier²,

Péqueux³

et al. 2005

Journal of Neuroimmunology

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Ontogenesis of oxytocin (OT) and vasopressin (VP) gene expression and function were investigated in murine thymus. OT and VP transcripts were detected in the thymus on embryonic days 13 and 15, respectively. Corresponding messenger RNAs were evidenced in thymic epithelial cells by in situ hybridization with a neurophysin probe. From all OT and VP receptors, only OTR was expressed by all Tcell subsets, while V1bR was found in double positive and single positive CD8 cells. In fetal thymic organ cultures, OTR antagonist d [dTyr(Et) 2 , Thr 4 ]OVT increased early apoptosis of CD8 cells, while V1bR antagonist (Sanofi SSR149415) inhibited T-cell differentiation, and favored CD8 T-cell commitment. D

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Cryptocrine signaling in the thymus network and T cell education to neuroendocrine self-antigens

Cited by 10 publications

References 41 publications

Thymic Expression of the Pancreatic Endocrine Hormones

Thymic Expression of the Pancreatic Endocrine Hormones

Corticotropin‐Releasing Hormone Immunoreactivity in Human T and B Cells and Macrophages: Colocalization With Arginine Vasopressin

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

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