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Foxo: in command of T lymphocyte homeostasis tolerance

Immunology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
Trends in Immunology (Impact Factor: 12.03). 01/2011; 32(1):26-33. DOI: 10.1016/j.it.2010.10.005
Source: PubMed

ABSTRACT The forkhead box O (Foxo) family of transcription factors consists of the mammalian orthologs of the Caenorhabditis elegans longevity protein Daf-16, and has an evolutionarily conserved function in the regulation of nutrient sensing and stress responses. Recent studies have shown that Foxo proteins control expression of immune system-specific genes such as Il7ra in naïve T cells and Foxp3 in regulatory T cells, which are crucial regulators of T cell homeostasis and tolerance. These findings reveal that the ancient Foxo pathway has been co-opted to regulate highly specialized T cell activities. The Foxo pathway probably enables a diverse and self-tolerant population of T cells in the steady state, which is an important prerequisite for the establishment of a functional adaptive immune system.

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    • "A number of other sequence-specific transcription factors have also been implicated in Treg development and function. These include the factors that promote FoxP3 expression during development or homoeostasis (such as FOXO, NF-kb, GATA3 and FOXP3 itself) and those that direct Treg functional specialization in response to inflammatory cues (such as T-BET, IRF4 and STAT3 selectively required for Tregs to suppress Th1-, Th2-and Th17-type inflammation, respectively) (Chaudhry et al, 2009; Koch et al, 2009; Long et al, 2009; Zheng et al, 2009; Kerdiles et al, 2010; Ouyang et al, 2010; Zheng et al, 2010; Ouyang and Li, 2011; Wang et al, 2011). Much less is known regarding the transcription programme that controls Treg activation, even though Treg activation is essential for Treg function. "
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    • "During the review of this manuscript, and consistent with this contention, two reports appeared showing that Foxo1 plays a role in the direct transcriptional control of Foxp3 (Ouyang et al., 2010; Harada et al., 2010). We note however, that within the population of Foxp3 + Foxo1 deficient T cells, the amount of Foxp3 per cell was only marginally decreased. "
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