{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T18:16:26Z","timestamp":1760984186073,"version":"3.40.3"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2011,11,1]],"date-time":"2011-11-01T00:00:00Z","timestamp":1320105600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The activity of acid sphingomyelinase (aSMase) was previously reported to be involved in glucocorticoid-induced cell death (GICD) of T lymphocytes. This mechanism in turn is believed to contribute to the therapeutic efficacy of glucocorticoids (GCs) in the treatment of inflammatory diseases. In this study, we reassessed the role of aSMase in GICD by using aSMase knockout mice. The absence of aSMase largely abolished the partial protection that effector memory CD4+ T cells in wild-type mice possess against GICD. Reduced IL-2 secretion by aSMase-deficient CD4+ T cells suggested that a lack of this important survival factor might be the cause of these cells\u2019 enhanced susceptibility to GICD. Indeed, addition of IL-2 restored the protection against GICD, whereas neutralization of IL-2 abrogated the otherwise protective effect seen in wild-type effector memory CD4+ T cells. The therapeutic implications of the altered sensitivity of aSMase-deficient T cells to GICD were assessed in models of inflammatory disorders; namely, experimental autoimmune encephalomyelitis and acute graft-versus-host disease. Surprisingly, GC treatment was equally efficient in both models in terms of ameliorating the diseases, regardless of the genotype of the T cells. Thus, our data reveal a hitherto unrecognized contribution of aSMase to the sensitivity of effector memory CD4+ T cells to GICD and call into question the traditionally attributed importance of GICD of T cells to the treatment of inflammatory diseases by GCs.<\/jats:p>","DOI":"10.4049\/jimmunol.1100911","type":"journal-article","created":{"date-parts":[[2011,9,24]],"date-time":"2011-09-24T06:44:21Z","timestamp":1316846661000},"page":"4509-4516","source":"Crossref","is-referenced-by-count":25,"title":["Acid Sphingomyelinase Is Required for Protection of Effector Memory T Cells against Glucocorticoid-Induced Cell Death"],"prefix":"10.1093","volume":"187","author":[{"given":"Denise","family":"Tischner","sequence":"first","affiliation":[{"name":"Department of Cellular and Molecular Immunology, University of G\u00f6ttingen Medical School , G\u00f6ttingen 37073 ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Theiss","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Immunology, University of G\u00f6ttingen Medical School , G\u00f6ttingen 37073 ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Karabinskaya","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Immunology, University of G\u00f6ttingen Medical School , G\u00f6ttingen 37073 ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jens","family":"van den Brandt","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Immunology, University of G\u00f6ttingen Medical School , G\u00f6ttingen 37073 ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sybille D","family":"Reichardt","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Immunology, University of G\u00f6ttingen Medical School , G\u00f6ttingen 37073 ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrike","family":"Karow","sequence":"additional","affiliation":[{"name":"Institute for Medical Microbiology, Immunology and Hygiene, Medical Center, University of Cologne , Cologne 50935 ,","place":["Germany"]},{"name":"Center for Molecular Medicine University of Cologne , Cologne 50935 ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco J","family":"Herold","sequence":"additional","affiliation":[{"name":"Institute of Virology and Immunobiology, University of W\u00fcrzburg , W\u00fcrzburg 97078 ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fred","family":"L\u00fchder","sequence":"additional","affiliation":[{"name":"Department of Neuroimmunology, Institute for Multiple Sclerosis Research and Hertie Foundation, University of G\u00f6ttingen Medical School , G\u00f6ttingen 37073 ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olaf","family":"Uterm\u00f6hlen","sequence":"additional","affiliation":[{"name":"Institute for Medical Microbiology, Immunology and Hygiene, Medical Center, University of Cologne , Cologne 50935 ,","place":["Germany"]},{"name":"Center for Molecular Medicine University of Cologne , Cologne 50935 ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Holger M","family":"Reichardt","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Immunology, University of G\u00f6ttingen Medical School , G\u00f6ttingen 37073 ,","place":["Germany"]},{"name":"Institute of Virology and Immunobiology, University of W\u00fcrzburg , W\u00fcrzburg 97078 ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2011,11,1]]},"reference":[{"key":"2025032410442048900_r1","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1615\/CritRevImmunol.v29.i3.50","article-title":"Traditional concepts and future avenues of glucocorticoid action in experimental autoimmune encephalomyelitis and multiple sclerosis therapy","volume":"29","author":"L\u00fchder","year":"2009","journal-title":"Crit. 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