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

First Author  So T Year  2006
Journal  Proc Natl Acad Sci U S A Volume  103
Issue  10 Pages  3740-5
PubMed ID  16501042 Mgi Jnum  J:107141
Mgi Id  MGI:3620342 Doi  10.1073/pnas.0600205103
Citation  So T, et al. (2006) Signals from OX40 regulate nuclear factor of activated T cells c1 and T cell helper 2 lineage commitment. Proc Natl Acad Sci U S A 103(10):3740-5
abstractText  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. Naive 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 naive T cell. This action is not dependent on either IL-4R or IL-2R signals and results in OX40 controlling initial naive 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.
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