An essential role for c-FLIP in the efficient development of mature T lymphocytes.
Apoptosis-related genes play important roles in thymocyte maturation. We show that cellular FLICE-like inhibitory protein (c-FLIP), a procaspase-8-like apoptotic regulator, plays an essential role in the efficient development of mature T lymphocytes. Mice conditionally lacking c-FLIP in T lymphocytes display severe defects in the development of mature T cells, as indicated by a dramatically reduced number of CD4+ and CD8+ T cells in the spleen and lymph nodes of mutant mice. The impaired T lymphocyte maturation in c-FLIP conditional knockout mice occurs at the single-positive thymocyte stage and may be caused by enhanced apoptosis in vivo. Moreover, although c-FLIP has been implicated in T cell receptor signaling through nuclear factor (NF)-kappaB and Erk pathways, activation of NF-kappaB and Erk in c-FLIP-deficient thymocytes appears largely intact. Collectively, our data suggest that the primary role of c-FLIP in thymocyte maturation is to protect cells from apoptosis.
Zhang
Nu
N
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
He
You-Wen
YW
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D013154:Spleen / Q000166:cytology / Q000502:physiology; D013950:Thymus Gland / Q000166:cytology / Q000502:physiology
D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506387:Cflar protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D011948:Receptors, Antigen, T-Cell; D048049:Extracellular Signal-Regulated MAP Kinases