Functional study of WW domain-containing oxidoreductase in T cells

Abstract

Event Abstract Back to Event Functional study of WW domain-containing oxidoreductase in T cells Tsung-Hao Chang1 and Li-Jin Hsu2* 1 National Cheng Kung University, The Institute of Basic Medical Sciences, Taiwan 2 National Cheng Kung University, Department of Medical Laboratory Science and Bio Technology, Taiwan WW domain-containing oxidoreductase (known as WOX1) has been shown to promote stress-induced cancer cell death and function as a tumor suppressor. Previous studies indicated that WOX1-deficient mice exhibit preweaning lethality, abnormal bone formation and growth retardation. However, whether WOX1 plays a role in the immune system is unknown. In this study, we investigated the functional role of WOX1 in lymphoid organs and found thymus atrophy in WOX1-deficient mice. Using cleaved caspase-3 staining and TUNEL assay, we examined higher levels of caspase activation and apoptosis in WOX1-deficient thymus. After ex vivo culture for 24 hours, WOX1-deficient thymocytes showed higher percentages of cell death than control, as determined by annexin-V and propidium iodide staining. The presence of a pan-caspase inhibitor, Z-VAD, in cultures partially prevented apoptosis in WOX1-deficient thymocytes. These results suggest that WOX1-deficient thymocytes are prone to cell death. To explore the intrinsic or extrinsic defect that causes extensive apoptosis in WOX1-deficient thymocytes, wild-type or WOX1-deficient bone marrow cells carrying CD45.2 were transferred into CD45.1+ NOD.SCID mice. Our results demonstrated that wild-type bone marrow cells differentiated into mature T cells and showed normal distribution of thymocyte subpopulations in NOD.SCID recipients 6 weeks after adoptive transfer. However, WOX1-deficient bone marrow cells failed to differentiate into mature T cells in recipient mice. In summary, we show here that WOX1-deficient thymocytes exhibit intrinsic defects in sustaining cell differentiation and survival. These in vivo findings run against the role of WOX1 as a pro-apoptotic protein and unravel a novel function of WOX1 in thymocyte development. Keywords: WW domain-containing oxidoreductase, T cells, thymocyte development, tumor suppressor, Cell Death Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Adaptive Immunity Citation: Chang T and Hsu L (2013). Functional study of WW domain-containing oxidoreductase in T cells. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.01016 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 30 Jun 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Li-Jin Hsu, National Cheng Kung University, Department of Medical Laboratory Science and Bio Technology, Tainan, Taiwan, hsu.lijin@gmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Tsung-Hao Chang Li-Jin Hsu Google Tsung-Hao Chang Li-Jin Hsu Google Scholar Tsung-Hao Chang Li-Jin Hsu PubMed Tsung-Hao Chang Li-Jin Hsu Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.