Sustained expression of pre-TCR induced beta-catenin in post-beta-selection thymocytes blocks T cell development.

The Journal of Immunology : Official Journal of the American Association of Immunologists
Mai XuJyoti Misra Sen

Abstract

Pre-TCR and IL-7R signals regulate beta-selection of thymocytes and then must be down-regulated for further development. However, the molecular events that control down-regulation remain unknown. We and others have previously shown that beta-catenin in cooperation with TCF regulates beta-selection. In this paper, we demonstrate that beta-catenin expression is stringently regulated by intrathymic signals, it is expressed at the highest levels in the pre-TCR signaled thymocytes, and is down-regulated in post-beta-selection thymocytes. Pre-TCR-induced beta-catenin regulates initial stages of pre-TCR signaling including expression of early growth response (Egr) genes but must be down-regulated to express RORgammat, which is essential for maturation to the CD4+CD8+ double positive (DP) stage. Sustained expression of beta-catenin results in the generation of IL-7R-, Egr-, and TGFbeta-expressing pre-DP thymocytes that are blocked in development. These data are consistent with a model in which post-beta-selection, pre-TCR-induced beta-catenin expression must return to background levels for efficient transition to the DP stage.

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Citations

Apr 12, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Archna SharmaJyoti Misra Sen
Apr 22, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Divya K Shah, Juan Carlos Zúñiga-Pflücker
Mar 25, 2014·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Sara Ferrando-MartínezManuel Leal
Oct 26, 2010·Immunological Reviews·Ellen V RothenbergLong Li
Apr 27, 2012·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Jian MaZuoming Sun
Nov 28, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Chunshu WongPan Zheng
Jan 19, 2010·Immunologic Research·Qing YuJyoti Misra Sen
Sep 24, 2010·PloS One·Matthew Lovatt, Marie-José Bijlmakers
Jul 26, 2014·Nature Reviews. Immunology·Mary A Yui, Ellen V Rothenberg
May 22, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nesrine MaharziBruno Canque

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