c-FLIP Expression in Foxp3-Expressing Cells Is Essential for Survival of Regulatory T Cells and Prevention of Autoimmunity.

2.50
Hdl Handle:
http://hdl.handle.net/10033/621002
Title:
c-FLIP Expression in Foxp3-Expressing Cells Is Essential for Survival of Regulatory T Cells and Prevention of Autoimmunity.
Authors:
Plaza-Sirvent, Carlos; Schuster, Marc; Neumann, Yvonne; Heise, Ulrike; Pils, Marina C; Schulze-Osthoff, Klaus; Schmitz, Ingo ( 0000-0002-5360-0419 )
Abstract:
Regulatory T (Treg) cells are critical for the shutdown of immune responses and have emerged as valuable targets of immunotherapies. Treg cells can rapidly proliferate; however, the homeostatic processes that limit excessive Treg cell numbers are poorly understood. Here, we show that, compared to conventional T cells, Treg cells have a high apoptosis rate ex vivo correlating with low c-FLIP expression. Treg-specific deletion of c-FLIP in mice resulted in fatal autoimmune disease of a scurfy-like phenotype characterized by absent peripheral Treg cells, activation of effector cells, multi-organ immune cell infiltration, and premature death. Surprisingly, blocking CD95L did not rescue Treg survival in vivo, suggesting additional survival functions of c-FLIP in Treg cells in addition to its classical role in the inhibition of death receptor signaling. Thus, our data reveal a central role for c-FLIP in Treg cell homeostasis and prevention of autoimmunity.
Affiliation:
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
Citation:
c-FLIP Expression in Foxp3-Expressing Cells Is Essential for Survival of Regulatory T Cells and Prevention of Autoimmunity. 2017, 18 (1):12-22 Cell Rep
Journal:
Cell reports
Issue Date:
3-Jan-2017
URI:
http://hdl.handle.net/10033/621002
DOI:
10.1016/j.celrep.2016.12.022
PubMed ID:
28052242
Type:
Article
Language:
en
ISSN:
2211-1247
Appears in Collections:
publications of the AG system-oriented immunologyand infection research (SIME)

Full metadata record

DC FieldValue Language
dc.contributor.authorPlaza-Sirvent, Carlosen
dc.contributor.authorSchuster, Marcen
dc.contributor.authorNeumann, Yvonneen
dc.contributor.authorHeise, Ulrikeen
dc.contributor.authorPils, Marina Cen
dc.contributor.authorSchulze-Osthoff, Klausen
dc.contributor.authorSchmitz, Ingoen
dc.date.accessioned2017-07-11T08:54:20Z-
dc.date.available2017-07-11T08:54:20Z-
dc.date.issued2017-01-03-
dc.identifier.citationc-FLIP Expression in Foxp3-Expressing Cells Is Essential for Survival of Regulatory T Cells and Prevention of Autoimmunity. 2017, 18 (1):12-22 Cell Repen
dc.identifier.issn2211-1247-
dc.identifier.pmid28052242-
dc.identifier.doi10.1016/j.celrep.2016.12.022-
dc.identifier.urihttp://hdl.handle.net/10033/621002-
dc.description.abstractRegulatory T (Treg) cells are critical for the shutdown of immune responses and have emerged as valuable targets of immunotherapies. Treg cells can rapidly proliferate; however, the homeostatic processes that limit excessive Treg cell numbers are poorly understood. Here, we show that, compared to conventional T cells, Treg cells have a high apoptosis rate ex vivo correlating with low c-FLIP expression. Treg-specific deletion of c-FLIP in mice resulted in fatal autoimmune disease of a scurfy-like phenotype characterized by absent peripheral Treg cells, activation of effector cells, multi-organ immune cell infiltration, and premature death. Surprisingly, blocking CD95L did not rescue Treg survival in vivo, suggesting additional survival functions of c-FLIP in Treg cells in addition to its classical role in the inhibition of death receptor signaling. Thus, our data reveal a central role for c-FLIP in Treg cell homeostasis and prevention of autoimmunity.en
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titlec-FLIP Expression in Foxp3-Expressing Cells Is Essential for Survival of Regulatory T Cells and Prevention of Autoimmunity.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.en
dc.identifier.journalCell reportsen

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