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

Plaza-Sirvent, Carlos; Schuster, Marc; Neumann, Yvonne; Heise, Ulrike; Pils, Marina C; Schulze-Osthoff, Klaus; Schmitz, Ingo

dc.contributor.author	Plaza-Sirvent, Carlos
dc.contributor.author	Schuster, Marc
dc.contributor.author	Neumann, Yvonne
dc.contributor.author	Heise, Ulrike
dc.contributor.author	Pils, Marina C
dc.contributor.author	Schulze-Osthoff, Klaus
dc.contributor.author	Schmitz, Ingo
dc.date.accessioned	2017-07-11T08:54:20Z
dc.date.available	2017-07-11T08:54:20Z
dc.date.issued	2017-01-03
dc.identifier.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	en
dc.identifier.issn	2211-1247
dc.identifier.pmid	28052242
dc.identifier.doi	10.1016/j.celrep.2016.12.022
dc.identifier.uri	http://hdl.handle.net/10033/621002
dc.description.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.
dc.language.iso	en	en
dc.rights.uri	http://creativecommons.org/licenses/by-nc-sa/4.0/	*
dc.title	c-FLIP Expression in Foxp3-Expressing Cells Is Essential for Survival of Regulatory T Cells and Prevention of Autoimmunity.	en
dc.type	Article	en
dc.contributor.department	Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.	en
dc.identifier.journal	Cell reports	en
refterms.dateFOA	2017-07-03T00:00:00Z
html.description.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.