c-FLIP Expression in Foxp3-Expressing Cells Is Essential for Survival of Regulatory T Cells and Prevention of Autoimmunity
In: Cell Reports, Jg. 18 (2017), Heft 1, S. 12-22
Online
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Zugriff:
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.
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c-FLIP Expression in Foxp3-Expressing Cells Is Essential for Survival of Regulatory T Cells and Prevention of Autoimmunity
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Autor/in / Beteiligte Person: | Schulze-Osthoff, Klaus ; Pils, Marina C. ; Heise, Ulrike ; Schuster, Marc ; Plaza-Sirvent, Carlos ; Neumann, Yvonne ; Schmitz, Ingo ; Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany. |
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Zeitschrift: | Cell Reports, Jg. 18 (2017), Heft 1, S. 12-22 |
Veröffentlichung: | Elsevier BV, 2017 |
Medientyp: | unknown |
ISSN: | 2211-1247 (print) |
DOI: | 10.1016/j.celrep.2016.12.022 |
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