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c-FLIP Expression in Foxp3-Expressing Cells Is Essential for Survival of Regulatory T Cells and Prevention of Autoimmunity.
- Source :
-
Cell reports [Cell Rep] 2017 Jan 03; Vol. 18 (1), pp. 12-22. - Publication Year :
- 2017
-
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.<br /> (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Antibodies, Blocking pharmacology
Caspase Inhibitors pharmacology
Cell Death drug effects
Cell Survival drug effects
Fas Ligand Protein metabolism
Gene Deletion
Lymph Nodes cytology
Mice
Phenotype
Spleen cytology
T-Lymphocytes, Regulatory drug effects
fas Receptor metabolism
Autoimmunity drug effects
CASP8 and FADD-Like Apoptosis Regulating Protein metabolism
Forkhead Transcription Factors metabolism
T-Lymphocytes, Regulatory immunology
Subjects
Details
- Language :
- English
- ISSN :
- 2211-1247
- Volume :
- 18
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 28052242
- Full Text :
- https://doi.org/10.1016/j.celrep.2016.12.022