Oncotarget

Research Papers: Immunology:

Schlafen2 mutation unravels a role for chronic ER stress in the loss of T cell quiescence

Ibrahim Omar, Antonio Lapenna, Leonor Cohen-Daniel, Boaz Tirosh and Michael Berger _

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Oncotarget. 2016; 7:39396-39407. https://doi.org/10.18632/oncotarget.9818

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Abstract

Ibrahim Omar1, Antonio Lapenna1, Leonor Cohen-Daniel1, Boaz Tirosh2 and Michael Berger1

1 The Lautenberg Center for Immunology and Cancer Research, The Biomedical Research Institute Israel-Canada of the Faculty of Medicine, The Hebrew University Hadassah Medical School, Jerusalem, Israel

2 Institute for Drug Research, School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel

Correspondence to:

Michael Berger, email:

Keywords: ER stress, UPR, Slfn2, quiescence, XBP1, Immunology and Microbiology Section, Immune response, Immunity

Received: May 08, 2016 Accepted: May 22, 2016 Published: June 03, 2016

Abstract

Immunologically naïve lymphocytes are kept in a quiescent state until antigen engagement. These quiescent immune cells are characterized by small cell size, lack of spontaneous proliferation and low metabolic rate. Lymphocyte quiescence is actively enforced condition which ensures the preservation of proper differentiation and proliferation capabilities of naïve and memory lymphocytes. Previously we described a chemically induced mutation in Schlafen2 (Slfn2), termed elektra, which breaks quiescence and compromises immunity. However, the mechanism by which Slfn2 maintains quiescence remains unknown. Here we demonstrate that elektra T cells display chronic ER stress under steady state conditions. Modulation of ER stress response by depletion of either UPR mediators XBP1 or CHOP, improved viability and partially corrected the developmental abnormalities and proliferation capabilities of elektra T cells. Altogether, our results demonstrate a functional connection between Slfn2 induced quiescence in T cells and ER homeostasis, clarifying a novel mechanism by which immune cell quiescence is maintained.


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