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Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, Vol. 92 No. 10 (November 15), 1998: pp. 3745-3755 Thymocyte Contact or Monoclonal Antibody-Mediated Clustering of 31 or 64 Integrins Activate Interleukin-6 (IL-6) Transcription Factors (NF-B and NF-IL6) and IL-6 Production in Human Thymic Epithelial Cells Dunia Ramarli, Maria Teresa Scupoli, Emma Fiorini, Ornella Poffe, Monica Brentegani, Antonello Villa, Germana Cecchini, Giuseppe Tridente, and Pier Carlo Marchisio From the Institute of Immunology and Infectious Diseases, University of Verona, Verona, Italy; DIBIT, Department of Biological and Technological Research, San Raffaele Scientific Institute, Milano, Italy; Clinical Immunology, Azienda Ospedaliera Verona, Verona, Italy; and the Department of Biomedical Sciences and Human Oncology, University of Torino School of Medicine, Torino, Italy. T-cell precursors develop within the thymus in contact with multiple supportive elements, among which thymic epithelial cells (TEC) are known to exert a dominant role in their homing, survival, and functional differentiation. All these functions are supported by cell-cell contacts and cytokine release. Signaling events triggered in lymphoid cells by adhesion to TEC are well characterized, but little is known about the opposite phenomenon. To address this issue, we derived cultures of TEC from human normal thymus. TEC monolayers were cocultured with thymocytes and immunostained with monoclonal antibodies (MoAbs) to integrin (2, 3, 4, and 6) and  (1 and 4) chains. Optical and confocal analysis showed that integrins were polarized on TEC at discrete surface locations: 64 lined the basal surface of TEC monolayers, whereas 31 was found mostly at TEC-TEC contacts; it is noteworthy that both 31 and 64 became highly enriched also at the boundaries with adherent thymocytes. Functional studies performed with MoAbs anti-1 and -4 integrins showed that 1, and, to a much lower extent, 4 heterodimers are involved in the TEC-thymocyte adhesion. Thymocyte contact or MoAb-mediated ligation of 3, 6, 1, and 4 integrins was investigated as a potential inducer of intracellular signaling in TEC. Thymocyte adhesion or cross-linking of MoAbs bound to integrins clustered at the TEC/thymocyte contact sites led to activation of interleukin-6 (IL-6) gene transcription factors, namely NF-IL6 serine phosphorylation and NF-B nuclear targeting, as well as to increased IL-6 secretion. We propose that integrin clustering occurring during TEC-thymocyte contacts modulates in TEC the gene expression of a cytokine involved in thymocyte growth and functional differentiation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. Wilhelmsen, S. H.M. Litjens, and A. 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Levitan RPTP{micro} and protein tyrosine phosphorylation regulate K+ channel mRNA expression in adult cardiac myocytes Am J Physiol Cell Physiol, February 1, 2000; 278(2): C397 - C403. [Abstract] [Full Text] [PDF] M. Scupoli, E Fiorini, P. Marchisio, O Poffe, E Tagliabue, M Brentegani, G Tridente, and D Ramarli Lymphoid adhesion promotes human thymic epithelial cell survival via NF-(kappa)B activation J. Cell Sci., January 1, 2000; 113(1): 169 - 177. [Abstract] [PDF]

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