Signals from OX40 regulate nuclear factor of activated T cells c1 and T cell helper 2 lineage commitment

Takanori So, Jianxun Song, Katsuji Sugie, Amnon Altman, Michael Croft

研究成果: Article査読

91 被引用数 (Scopus)

抄録

T cell helper type 2 (Th2) differentiation is driven by a source of IL-4 receptor (IL-4R) that mobilizes IL-4R signaling pathways and the transcription factor GATA-3. Naïve CD4 cells can secrete IL-4 independently of IL-4R signals, but how this secretion is regulated is not understood. Here we demonstrate that costimulation through the tumor necrosis factor receptor family molecule OX40, in synergy with CD28, is essential for high levels of nuclear factor of activated T cells c1 to accumulate in the nucleus of a recently activated naïve T cell. This action is not dependent on either IL-4R or IL-2R signals and results in OX40 controlling initial naïve T cell IL-4 transcription. OX40 signals subsequently enhance nuclear GATA-3 accumulation through an IL-4R-dependent action, leading to Th2 differentiation. These data show that, in the absence of an exogenous source of IL-4, OX40 provides a critical synergistic and temporal signal with other noncytokine receptors to modulate nuclear factor of activated T cells c1 and to promote optimal Th2 generation.

本文言語English
ページ(範囲)3740-3745
ページ数6
ジャーナルProceedings of the National Academy of Sciences of the United States of America
103
10
DOI
出版ステータスPublished - 2006 3 7

ASJC Scopus subject areas

  • 一般

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