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Cutting edge: Lymphoproliferation caused by Fas deficiency is dependent on the transcription factor eomesodermin.


ABSTRACT: A hallmark of autoimmune lymphoproliferative syndrome (ALPS), caused by mutation of the Fas death receptor, is massive lymphadenopathy from aberrant expansion of CD4(-)CD8(-) (double-negative [DN]) T cells. Eomesodermin (Eomes) is a member of the T-box family of transcription factors and plays critical roles in effector cell function and memory cell fitness of CD8(+) T lymphocytes. We provide evidence in this study that DN T cells exhibit dysregulated expression of Eomes in humans and mice with ALPS. We also find that T cell-specific deletion of Eomes prevents lymphoid hypertrophy and accumulation of DN T cells in Fas-mutant mice. Although Eomes has critical physiological roles in the function and homeostasis of CD8(+) T cells, overexpression of Eomes appears to enable pathological induction or expansion of unusual CD8-related T cell subsets. Thus, antagonism of Eomes emerges as a therapeutic target for DN T cell ablation in ALPS.

SUBMITTER: Kinjyo I 

PROVIDER: S-EPMC2997140 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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Cutting edge: Lymphoproliferation caused by Fas deficiency is dependent on the transcription factor eomesodermin.

Kinjyo Ichiko I   Gordon Scott M SM   Intlekofer Andrew M AM   Dowdell Kennichi K   Mooney Erin C EC   Caricchio Roberto R   Grupp Stephan A SA   Teachey David T DT   Rao V Koneti VK   Lindsten Tullia T   Reiner Steven L SL  

Journal of immunology (Baltimore, Md. : 1950) 20101112 12


A hallmark of autoimmune lymphoproliferative syndrome (ALPS), caused by mutation of the Fas death receptor, is massive lymphadenopathy from aberrant expansion of CD4(-)CD8(-) (double-negative [DN]) T cells. Eomesodermin (Eomes) is a member of the T-box family of transcription factors and plays critical roles in effector cell function and memory cell fitness of CD8(+) T lymphocytes. We provide evidence in this study that DN T cells exhibit dysregulated expression of Eomes in humans and mice with  ...[more]

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